Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 27, 2026.

Akkermansia muciniphila : is it the Holy Grail for ameliorating metabolic diseases?

Juan Yan, Lili Sheng, Houkai Li

Gut Microbes · 2021 · Review

doi:10.1080/19490976.2021.1984104 (opens in a new tab)

Abstract

The increasing prevalence of metabolic diseases has become a severe public health problem. Gut microbiota play important roles in maintaining human health by modulating the host’s metabolism. Recent evidences demonstrate that Akkermansia muciniphila is effective in improving metabolic disorders and is thus considered as a promising “next-generation beneficial microbe”. In addition to the live A. muciniphila, similar or even stronger beneficial effects have been observed in pasteurized A. muciniphila and its components, including the outer membrane protein Amuc_1100, A. muciniphila-derived extracellular vesicles (AmEVs), and secreted protein P9. Hence, this paper presents a systemic review of recent progress in the effects and mechanisms of A. muciniphila and its components in the treatment of metabolic diseases, including obesity, type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, as well as perspectives on its future study.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 27, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

The prevalence of metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and nonalcoholic fatty liver disease (NAFLD) has becoming a severe public health problem:, Gut microbiota can regulate host metabolism by influencing immune maturation and homeostasis, protecting against pathogen overgrowth, regulating intestinal endocrine functions and neurologic signaling, modulating energy metabolism, and producing functional metabolites., The compositional and metabolic changes of intestinal microbiota (dysbiosis) is closely involved in the occurrence of metabolic diseases., Thus, considerable attention has been paid to gut microbiota-targeted therapies on metabolic diseases with diverse approaches, including probiotics, prebiotics, fecal microbiota transplantation, and antibiotics.

Akkermansia muciniphila, a commensal bacterium, is an oval-shaped, non-motile bacterium with no endospore formation, and a microaerophilic microbe that was first isolated from human feces in 2004. It colonizes in the intestinal tract early in life, and accounts for approximately 1–3% of the total intestinal microbiota in healthy adults. A. muciniphila resides in the intestinal mucus layer, utilizing the mucin as the sole source of carbon, nitrogen, and energy. In recent years, A. muciniphila has attracted much attention for its comprehensive roles in maintaining host wellbeing, which is regarded as a promising “next-generation beneficial microbe” for metabolic disease prevention or therapy owing to its various properties, including producing short-chain fatty acids (SCFAs),,, improving intestinal integrity,, and reducing endotoxemia through inhibiting the translocation of lipopolysaccharide (LPS) from the intestine to circulation. However, the exact mechanisms underlying the benefits of A. muciniphila on metabolic diseases are complicated because similar effects have been observed on either live A. muciniphila or pasteurized A. muciniphila, their outer membrane proteins or secreted proteins, as well as extracellular vesicles. In these papers, we systemically reviewed the updated progress of A. muciniphila with respect to its role in metabolic diseases, and discussion on its future research direction as well.

A. muciniphila and obesity

In recent years, with the changes in people’s dietary habits and the increased availability of high calorie diet, overweightness and obesity have become one of the most serious health problems in the world. Manipulation of gut microbiota is a promising strategy for obesity prevention or therapy. The relative abundance of A. muciniphila is significantly reduced in high-fat diet (HFD)-fed obese mice or rats compared with their lean littermates, and negatively correlated with body fat mass and glucose intolerance (Table 1)., Nevertheless, inconsistent results have also been reported. For example, the copy number of A. muciniphila had an increased trend in high-fat and high-sucrose diet (HFHS)-fed mice without reaching a statistical significance when analyzed by qPCR. In addition, by 16s rRNA sequencing, Arias et al. found significantly increased relative abundance of Akkermansia genus in HFD-fed female C3HeB/FeJ mice. Interestingly, the dietary impacts on Akkermansia levels were found to be genetically dependent in mice: Akkermansia was decreased in 129S1/SvImJ mice, but was increased in A/J, NOD/LtJ, C57BL/6 J, and NZO/HILtJ mice after short-term HFHS intake. Thus, the divergent genetically susceptible to intestinal microenvironment might account for the different response of A. muciniphila abundance to diet in the host. In clinical studies, a decreased abundance of A. muciniphila occurred in adults and children with obesity of both sexes. Furthermore, studies indicated that the reduced A. muciniphila in patients with obesity was independent of other metabolic diseases, including diabetes and NAFLD.,,, In contrast, an increase in A. muciniphila abundance was observed in children with obesity compared to children with normal-weight. Despite some inconsistent findings, the majority of studies in both animal and clinical studies support the negative correlation between A. muciniphila and obesity.

Given this negative correlation, the role of A. muciniphila in obesity has been widely investigated in both mice and human subjects. Everard et al. reported that administration of A. muciniphila reversed a series of disorders in HFD-fed mice, including reducing body weight, relieving insulin resistance, and fasting hyperglycemia, as well as increasing the mRNA expression of genes involved in the regulation of adipocyte differentiation and lipid oxidation. From that on, many research teams further found live or even pasteurized A. muciniphila as well as its components, including the outer membrane protein Amuc_1100, A. muciniphila-derived extracellular vesicles (AmEVs), and secreted protein P9, were effective in improving diet-induced obesity.,,,,,,,,,, These findings were summarized in Table 2. The benefits of A. muciniphila in obesity intervention has also been investigated in one clinical trial. Depommier et al. compared the safety and efficacy of live and pasteurized A. muciniphila in adults with overweight or obesity. Their results showed that daily oral supplementation of 1010 CFU of live or pasteurized A. muciniphila for three months was safe and well tolerated. However, improved insulin sensitivity, reduced insulinemia, and plasma total cholesterol was only present in patients given pasteurized A. muciniphila supplementation. This prospective study showed the feasibility to administer A. muciniphila to obese humans, however, further study is needed to demonstrate the relationship between supplement of A. muciniphila and improvement of metabolic parameters on a larger scale of subjects.

A. muciniphila and T2DM

T2DM is a common metabolic disease, which is genetic susceptible and obesity-oriented. In addition to well-recognized genetic and environmental risk factors, gut dysbiosis has emerged as a new risk factor for T2DM development,, in which the decreased abundance of A. muciniphila was frequently observed in either diabetic mice, or patients with pre-diabetes or T2DM. Our previous study demonstrated that administration of A. muciniphila reduced the fasting blood glucose level in western diet-fed mice, suggesting that A. muciniphila contributes to T2DM recovery. Moreover, a series of studies have shown that A. muciniphila supplementation may regulate host lipoprotein metabolism, improve insulin sensitivity, and alleviate hepatic metabolic inflammation in mice.,, A recent clinical trial of a new probiotic formulation WBF-011, which contains A. muciniphila and another four bacterial strains as well as inulin, found that WBF-011 improved postprandial blood glucose in T2DM patients. This is the first randomized controlled trial to show the effect of A. muciniphila on improving T2DM in human subjects. In addition, the baseline abundance of A. muciniphila also affected the metabolic outcomes of calorie restriction: individuals with higher baseline A. muciniphila showed better responses toward calorie restriction than those who had low baseline A. muciniphila.

Interestingly, the alteration of A. muciniphila was also found to be involved in the anti-T2DM effect of metformin, a widely used first-line medicine for T2DM. Shin et al. reported that metformin significantly increased the abundance of A. muciniphila in HFD-fed mice, while oral supplementation of A. muciniphila to HFD-fed mice without metformin also improved glucose tolerance and reduced inflammation in adipose tissue. Cuesta-Zuluaga et al. found higher abundance of A. muciniphila in T2DM patients with metformin therapy than healthy subjects (Table 3). These results suggest that the elevated A. muciniphila contributes to the anti-T2DM effect of metformin, providing new understanding on the role of A. muciniphila. Overall, existing evidence highlights the significance of A. muciniphila in T2DM development, as well as its involvement in the anti-T2DM activity of clinical medicines.

A. muciniphila and CVD

CVD remains the leading cause of death worldwide, especially in western countries., The relationship between gut microbiota dysbiosis and CVD has been well determined., Dietary phosphatidylcholine or L-carnitine can be metabolized into trimethylamine (TMA) by the gut microbiota, and then transported to the liver, where TMA is converted into trimethylamine N-oxide (TMAO) by hepatic flavin monooxygenase 3 (FMO3). TMAO has been shown to be a potent trigger and biomarker for CVD., Recently, Plovier et al. reported that supplementation with A. muciniphila significantly increased the excretion of TMAO and TMA in urine, resulting in decreased plasma TMAO and TMA levels. In addition, they found that HFD induced two-fold higher FMO3 expression compared with that in control-diet fed mice, whereas treatment with pasteurized A. muciniphila could offset this change, suggesting pasteurized A. muciniphila intervention may also reduce TMAO production. Li et al. discovered that oral administration of live A. muciniphila reduced exacerbation of atherosclerotic lesion formation, as well as aortic and systemic inflammation induced by a western diet, and improved intestinal integrity in antherosclerotic Apoe−/− mice. These evidences indicate that A. muciniphila, live or pasteurized, has a protective effect against CVD development.

In addition to the co-metabolized TMA/TMAO pathway by host and gut microbiota, short-chain fatty acids (SCFAs), which can be generated by A. muciniphila, are also essential metabolites for bridging the crosstalk between A. muciniphila and host., The beneficial effects of SCFAs on host metabolism have been extensively investigated and reviewed in CVD., In summary, A. muciniphila may play a protective role in CVD development directly or through producing metabolites, and via crosstalk with host and commensal bacteria as well.

A. muciniphila and NAFLD

NAFLD is a chronic liver disease and hepatic manifestation of metabolic syndrome. The homeostasis of commensal bacteria and bacteria-derived molecules have been increasingly recognized as a key determinant of NAFLD. The association of A. muciniphila with NAFLD development was recently investigated in obese mice with NAFLD, in which a decreased abundance of A. muciniphila was observed. The administration of anti-obesity drug, such as liraglutide, decreased the levels of total cholesterol and triacylglycerol in the liver while increasing the abundance of A. muciniphila. A. muciniphila supplementation also decreased the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated liver histopathological damage in a mouse model. Kim et al. recently reported that oral administration of A. muciniphila prevented fatty liver disease by regulating the expression of genes that regulate fat synthesis and inflammation in the liver. Moreover, different genotypes of A. muciniphila, isolated from human stool samples, played different roles in HFD-induced hyperlipidemia and liver steatosis. Specifically, A. muciniphila I (Amuc_GP01, strain GP01 of A. muciniphila I) was more effective for alleviating hyperlipidemia, liver steatosis, and glucose tolerance than A. muciniphila II (Amuc_GP25, strain GP25 of A. muciniphila II) in dietary obese mice. Both two genotypes could improve the intestinal barrier, but the effect of A. muciniphila II on improving endotoxemia was not apparent, possibly because they have different characteristics of genes and functions, leading to the identification of specific target pathways and disparate roles. Overall, these results indicate that A. muciniphila may alleviate NAFLD by regulating lipid metabolism and reducing inflammation.

Production of SCFAs and cross-feeding with butyrate-producing bacteria

SCFAs, mainly acetate, propionate, and butyrate, are the principal products of carbohydrate and protein fermentation by gut microbiota. There are a large number of investigations on the diverse roles of SCFAs in host metabolism., A. muciniphila is also a potent generator of acetate, propionate, and oligosaccharides by fermenting mucin,, resulting in the activation of fatty acid receptors FFAR2/GPR41 and FFAR3/GPR43. Interestingly, GPR41 is involved in the microbiota-associated adiposity process, as regularly raised Gpr41−/− mice are leaner than wild-type mice, whereas this difference is not observed under germ-free (GF) conditions. Activation of GPR41 and GPR43 induces intestinal L cells to produce peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2). PYY acts on the gastrointestinal tract by modulating a series of physiological actions. It is a satiety signal released following meals, and decreasing food intake. GLP-1, one of the principal incretin hormones, promotes glucose-dependent insulinotropic activity, inhibits appetite and food intake, delays gastric emptying, and restores the impaired “incretin effect” in T2DM patients. Acetate could also promote anti-lipolytic activity through GPR43 in white adipose tissue (WAT). GPR43 stimulation by acetate in the WAT, rather than muscle or liver, also improves glucose and lipid metabolism. Propionate can be converted into glucose by intestinal gluconeogenesis (IGN), resulting in satiety and reduced hepatic glucose production. In addition, Lukovac et al. found that many transcription factors regulating lipid metabolism and proliferation, such as Hnf4α and p53 family members (Tp53 and Tp73), were affected by both A. muciniphila and propionate.

The biological function of A. muciniphila is also associated with cross-feeding activity with other butyrate-producing bacteria such as Faecalibacterium prausnitzii and Anaerostipes caccae, resulting in the increased production of butyrate., Moreover, acetate can also stimulate the growth of butyrate-producing bacteria within the same mucosal niche. Butyrate is not only a preferred energy source for colon cells, it also has various beneficial functions for the host, especially in metabolic diseases, and is a more potent agonist for GPR41 than acetate or propionate.

Overall, considering the facts that pasteurization of A. muciniphila enhanced its capacity to improve body weight, reduce fat mass development and dyslipidemia, and administration of Amuc_1100, AmEVs, and secreted P9 protein replicated part of the biological functions of live bacteria (Table 2), the beneficial effects of A. muciniphila might depend in part on its capacity of SCFAs production, as well as the cross-feeding relationship with other butyrate-producing bacteria in the gut.

Maintaining the integrity of gut barrier

A number of studies have revealed the correlation between obesity-related metabolic diseases and increased gut permeability, which induces metabolic endotoxemia and inflammation. A. muciniphila can considerably improve gut barrier integrity in obese mice by restoring the thickness of the intestinal mucus layer, and oral supplementation of A. muciniphila can increase the number of goblet cells, normalize the mucus thickness of the inner layer, and increase the expression of tight-junction proteins in the gut of both HFD-induced obese mice and mice with alcoholic fatty liver.,, Moreover, Li et al. discovered that A. muciniphila reduced intestinal permeability by increasing the expression of occludin and ZO-1 in Apoe−/− mice. Similarly, Zhao et al. reported that administration of A. muciniphila could reduce chronic low-grade inflammation by decreasing the permeability of the gut and lipopolysaccharide (LPS)-binding protein (LBP) downstream signaling in the liver and muscle. Reunanen et al. found that A. muciniphila could adhere to the intestinal epithelium and enhance enterocyte monolayer integrity in vitro, suggesting the ability of A. muciniphila to repair the damaged gut barrier. Furthermore, a large number of studies have shown that bacteria-derived SCFAs maintain the integrity of the intestinal tract and prevent the translocation of LPS across the intestinal wall to alleviate the systemic inflammatory response.,, Not only live A. muciniphila, but also pasteurized A. muciniphila has been found to enhance the gut barrier function, leading to attenuation of metabolic endotoxemia. In addition, Amuc_1100 elevated the development of transepithelial electrical resistance in Caco2-cells and increased the expression of tight junction genes in HFD-fed mice to improve intestinal barrier function., Moreover, administration of AmEVs also protected mice from HFD-induced leaky gut (Table 2).,

In addition, gut barrier function is disrupted in inflammatory bowel disease (IBD). As a mucin-degrader, A. muciniphila decreased significantly in dextran sulfate sodium (DSS)-induced colitis in mice and in IBD patients,, while administration of A. muciniphila or AmEVs have been reported to protect the progression of DSS-induced colitis. On the contrary, the abundance of A. muciniphila was found to be increased in the spontaneous colitis in the Il10−/− mice model of IBD, while supplementation of A. muciniphila further promoted colitis in this model. However, it should be noticed that these findings in immune compromised or genetic editing mouse models cannot be translated into the human situation directly. Although the role of A. muciniphila in colitis is somewhat contradictory based on these reports, most studies supported the potential benefits of A. muciniphila or its derived metabolites in respect to their functions of reducing metabolic endotoxemia and systemic inflammation of host, or improving the integrity of gut barrier. Further studies are also needed to determine the exact role of A. muciniphila, live or pasteurized, or its metabolites, in colitis.

Pasteurized A. muciniphila in metabolic disease

Although the beneficial effects of A. muciniphila on metabolic diseases have been extensively investigated,,, their clinical application is still challenging, owing to its microaerophilic requirements and the loss of activity after heat-killing. Meanwhile, its growth media probably contain animal-derived compounds, which may have viruses, allergens or bacterial contaminants, thus limiting the usage for clinical study. Plovier et al. showed that A. muciniphila retained its efficacy in improving metabolic disorders when grown on a synthetic medium, a replacement for animal derived mucins. Ottman et al. identified 79 putative outer membrane and membrane-associated extracellular proteins and 23 of those had different abundance between cells of A. muciniphila grown on mucin-containing media and those grown on the non-mucus glucose-containing media. Moreover, Shin et al. found that A. muciniphila grown under mucin-containing media upregulated genes encoding mucin-degrading enzymes. In contrast, A. muciniphila grown under mucin-depleted conditions upregulated the genes involved in glycolysis, energy metabolic pathways, and 79 genes encoding extracellular protein candidates including Amuc_1100, which, in turn, reduced obesity and improved intestinal barrier more efficiently than administration of A. muciniphila grown under mucin-containing conditions. These findings by different teams suggest mucin in the medium might affect the expression of outer membrane protein and subsequently influence the function of A. muciniphila. Interestingly, the recent study discovered that pasteurized A. muciniphila was more potent than live A. muciniphila for reducing body weight and improving glucose tolerance in HFD-induced obese mice. This is of great significance for clinical applications, and therefore, increased attention has been paid to the effect of pasteurized A. muciniphila on metabolic diseases in recent years. Zhang et al. found that oral administration of live or pasteurized A. muciniphila significantly increased the levels of plasma high-density lipoprotein (HDL) and decrease hepatic glycogen, as well as reduced inflammatory markers of LPS and TNF-α to alleviate systemic inflammation. However, oral administration of live or pasteurized A. muciniphila did not improve glucose levels in diabetic rats. Depommier et al. reported that daily oral supplementation of pasteurized A. muciniphila in a small number of subjects improved insulin sensitivity and decreased insulinemia and plasma total cholesterol compared to the placebo group, and the effects of pasteurized A. muciniphila were better than those of live A. muciniphila. Although this study only included a small number of participants, the results highlight the potential of pasteurized A. muciniphila in clinical applications. It is hypothesized that the effects of pasteurized A. muciniphila are attributed to increased energy excretion in feces, reduced carbohydrate absorption, and enhanced intestinal epithelial turnover, but without impacts on intestinal lipid absorption or chylomicron synthesis. In conclusion, these studies demonstrate that pasteurized A. muciniphila is superior to live ones for improving metabolic disorders in mice, rats, and humans; however, the underlying mechanism warrants further investigation.

A. muciniphila outer membrane protein enhances the gut barrier

In addition to the A. muciniphila itself, the identification of active components of A. muciniphila for the treatment of metabolic diseases is also valued recently. Cell derived fragments of A. muciniphila have been shown to activate Toll-like receptor 2 (TLR2), in which a highly abundant outer membrane pili-like protein of A. muciniphila, named Amuc_1100, with specific activating capacity for TLR2 has been identified by proteomics. TLRs regulate bacterial recognition, intestinal homeostasis, and shape host metabolism. Ottman et al. found that Amuc_1100 activated TLR 2 and TLR4 and significantly increased transepithelial electrical resistance in vitro. In line with the enhanced effects of pasteurized A. muciniphila, Amuc_1100 was found to be active after pasteurization. It has also been found that the expression of Cnr1, which codes cannabinoid receptor 1 (CB1) in the jejunum, was lower in Amuc_1100 treated mice. The downregulation of CB1 was associated with improved gut integrity and lipid accumulation induced by LPS in both liver and adipose tissue. Therefore, Amuc_1100 might contribute in part to the beneficial effect of live or pasteurized A. muciniphila on gut barrier function.

In addition to Amuc_1100, several other proteins of A. muciniphila have also been identified including Amuc_1434, Amuc_1686, Amuc_0771, and Amuc_1666. Meng et al. reported that Amuc_1434, a member of the aspartic protease family, degraded mucin2 protein secreted by LS174T and suppresses LS174T cell viability, suggesting its potential involvement in controlling colon cancer. Nevertheless, the roles of some β-galactosidases with mucin degradation capacity, such as Amuc_1686, Amuc_0771, and Amuc_1666, in regulating metabolic disorders remain unclear so far.,

A. muciniphila-derived extracellular vesicles (AmEVs) improve metabolic disorders

Emerging evidence shows that bacteria-derived extracellular vesicles, especially AmEVs, play important roles in mediating host-bacteria interactions.,, Chelakkot et al. analyzed the fecal extracellular vesicles of healthy people and individuals with obesity, and discovered that the feces of healthy individuals contained higher levels of AmEVs than individuals with obesity. They also revealed that oral gavage of AmEVs decreased HFD-induced body weight gain and fat mass, and improved metabolic functions and gut integrity. Ashrafian et al. also found that AmEVs ameliorated intestinal barrier impairment in obese mice. Moreover, AmEVs regulated inflammation and energy homeostasis in the colon of obese mice. Compared with A. muciniphila, oral gavage of AmEVs (10 μg/mouse) alleviated more body and fat weight gain as well as blood glucose and cholesterol levels in HFD-induced obese mice. In addition, AmEVs administration significantly reduced the expression of TLR-4 and induced lower TLR-2 expression in the colon tissue of obese mice. It is, however, improtant to note that AmEVs administration reducd daily food intake in this study. Additionally, the dose of AmEVs derived from how many A. muciniphila is unclear, and the relevant of the oral dose of AmEVs to physiological levels of AmEVs secreted by A. muciniphila in the gut is also unknown. Thus, the rationale for the dose used for AmEVs administration need to be further explored. Moreover, whether AmEVs contain Amuc_1100 or other effectors need further investigation. It has been reported that oral administration of AmEVs alleviated DSS-induced inflammatory bowel disease, characterized by reduced infiltration of inflammatory cells through the colon wall. Overall, these results suggest that AmEVs may protect the host by decreasing intestinal permeability and reducing inflammation in the gut. Therefore, the beneficial effects of the live bacteria may be, at least partly, due to AmEVs.

A. muciniphila-secreted protein ameliorates metabolic disease

Since administration of either the cell-free supernatantlive or live A. muciniphila, but not bacterial pellet, increased systemic GLP-1 secretion, Yoon et al. identified an 84 kDa protein in the culture supernatant, named P9, which accounts for the induction of GLP-1 secretion in HFD-fed mice and L cells. Administration of P9 to HFD-fed mice prevented obesity and improved glucose tolerance by regulating GLP-1 secretion and inducing brown adipose tissue thermogenesis. In terms of mechanism, ICAM-2 can bind to P9 and modulate P9-induced secretion of GLP-1. In addition, P9 strongly induced IL-6 expression and IL-6 dose-dependently increased GLP-1 secretion, wheares IL-6 deficiency downregulated the expression of ICAM-2 and blocked the response toward P9-induced GLP-1 secretion in mice, demostrating that P9 may improve metabolic diseases through an IL-6-GLP-1 signaling axis. Since pasteurized A. muciniphila and Amuc_1100 also have beneficial effects on regulating blood glucose,, P9 is not the only way for this bacterium to regulate glucose homeostasis. Cani and Knauf commented on this research and raised several important questions, such as how P9 acts on L cells to stimulate GLP-1 secretion and whether P9 is specific to A. muciniphila, etc. Further, in addtion to stimulating GLP-1 secretion, whether P9-mediated induction of IL-6 promotes inflammtaion in the gut and how it affects gut barrier function need to be illustrated.

Conclusions and perspectives

The current focus on improving health using gut microbiota-targeted strategies is overwhelming in the context of accumulating experimental and clinical evidence. A. muciniphila has emerged as a uniquely promising “next-generation beneficial microbe”, especially for metabolic disease management. A large number of studies have confirmed the alteration of A. muciniphila in both animal models and human patients with metabolic diseases (summarized in Table 1), its therapeutic benefits (summarized in Table 2), as well as the efficiency of interventions to boost its abundance (summarized in Table 3). However, most current animal studies with A. muciniphila supplementation were performed with A. muciniphila grown under mucin-containing conditions. The animal-derived mucin may introduce contaminants and cause compromised beneficial effect of A. muciniphila on alleviating metabolic diseases. Therefore, mucin-depleted media should be explored and given more attention for both animal and human investigations. Notably, most of the mechanistic studies on the effects of A. muciniphila were performed in animal models. Given the differences between animal models and humans in genetic and environmental elements, it is critical to investigate the real effects and mechanisms of A. muciniphila in clinical study. Recently, two randomized controlled trials confirmed that administration of A. muciniphila or A. muciniphila containing formulation WBF-011 to human subjects with obesity or T2DM were safe and well tolerated in a 12-week period with significant improvement in several metabolic paramaters., This paves the way for more clinical applications of A. muciniphila in the near future. The mechanisms underlying the effects of A. muciniphila on metabolic diseases have been extensively investigated and are summarized in Figure 1.

Given the similar, or even superior efficacy of pasteurized A. muciniphila and its outer membrane proteins such as Amuc_1100 or extracellular vesicles and secreted proteins, the exact mechanisms of A. muciniphila activity in the real world of complicated commensal systems is only beginning to be discovered. In this sense, we envisage several critical aspects for future studies on A. muciniphila. First, a complete understanding is required with regards to the common or differential mechanisms between live A. muciniphila and its derived products, including pasteurized A. muciniphila, or the active components such as proteins, vesicles, or metabolites released from the bacteria. Since it is unclear the equivalence of the doses used for AmEVs, P9, and other effectors with the physiological levels of A. muciniphila found in the gut, the physiological relevance of exact mechanisms of A. muciniphila activity need further exploration. Second, more efforts should be focused on elucidating the complex crosstalk between A. muciniphila and commensal bacteria, which may help to explain the discrepant results that have been observed in preclinical and clinical studies. Third, a deeper exploration of the relationship between the specificity in various conditions and the strains of A. muciniphila, rather than at the species level. Finally, scientists should always hold a reasonable dose of expectation and skepticism in terms of the overwhelming “good effects” of any potential beneficial microbe, including A. muciniphila, if the scientific basis has not been well established. Altogether, given the accumulating evidence of A. muciniphila on ameliorating metabolic disorders in both animals and humans, A. muciniphila is widely supposed to be one of the most promising microbes with multiple benefits for host metabolism. Although the mechanisms underlying the effects of A. muciniphila are largely unclear, identification and isolation of specific effectors and biomolecules that derived from A. muciniphila will pave the way for understanding the mechanisms of their action, which is essential and full of challenges for translation of the positive findings in animals to clinic application.

References 172

  1. 1.

    Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. Jama. 2015;313(19):1973–30. doi:.

    Not in our library10.1001/jama.2015.4260 (opens in a new tab)

  2. 2.

    Adeva-Andany MM, Rañal-Muíño E, Vila-Altesor M, Fernández-Fernández C, Funcasta-Calderón R, Castro-Quintela E. Dietary habits contribute to define the risk of type 2 diabetes in humans. Clin Nutr ESPEN. 2019:34:8-17. doi:.

    Not in our library10.1016/j.clnesp.2019.08.002 (opens in a new tab)

  3. 3.

    Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55–71. doi:.

    Not in our library10.1038/s41579-020-0433-9 (opens in a new tab)

  4. 4.

    Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375:2369–2379. doi:.

    Not in our library10.1056/nejmra1600266 (opens in a new tab)

  5. 5.

    Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda, Md). 2016;31:283–293. doi:.

    Not in our library10.1152/physiol.00041.2015 (opens in a new tab)

  6. 6.

    Aron-Wisnewsky J, Vigliotti C, Witjes J, Le P, Holleboom AG, Verheij J, Nieuwdorp M, Clément K. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nat Rev Gastroenterol Hepatol. 2020;17(5):279–297. doi:.

    Not in our library10.1038/s41575-020-0269-9 (opens in a new tab)

  7. 7.

    Angelakis E, Merhej V, Raoult D. Related actions of probiotics and antibiotics on gut microbiota and weight modification. Lancet Infect Dis. 2013;13:889–899. doi:.

    Not in our library10.1016/s1473-3099(13)70179-8 (opens in a new tab)

  8. 8.

    Rodriguez J, Hiel S, Neyrinck AM, Le Roy T, Pötgens SA, Leyrolle Q, Pachikian BD, Gianfrancesco MA, Cani PD, Paquot N, et al. Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients. Gut. 2020;69(11):1975–1987. doi:.

    Not in our library10.1136/gutjnl-2019-319726 (opens in a new tab)

  9. 9.

    Nicolucci AC, Hume MP, Martínez I, Mayengbam S, Walter J, Reimer RA. Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology. 2017;153:711–722. doi:.

    Not in our library10.1053/j.gastro.2017.05.055 (opens in a new tab)

  10. 10.

    Hong Y, Li B, Zheng N, Wu G, Ma J, Tao X, Chen L, Zhong J, Sheng L, Li H, et al. Integrated metagenomic and metabolomic analyses of the effect of astragalus polysaccharides on alleviating high-fat diet-induced metabolic disorders. Front Pharmacol. 2020;11:833. doi:.

    Not in our library10.3389/fphar.2020.00833 (opens in a new tab)

  11. 11.

    Wu TR, Lin CS, Chang CJ, Lin TL, Martel J, Ko YF, Ojcius DM, Lu -C-C, Young JD, Lai H-C, et al. Gut commensal parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from hirsutella sinensis. Gut. 2019;68:248–262. doi:.

    Not in our library10.1136/gutjnl-2017-315458 (opens in a new tab)

  12. 12.

    Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145(5):946–953. doi:.

    Not in our library10.1053/j.gastro.2013.08.058 (opens in a new tab)

  13. 13.

    Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(5):1469–1476. doi:.

    Not in our library10.1099/ijs.0.02873-0 (opens in a new tab)

  14. 14.

    Reunanen J, Kainulainen V, Huuskonen L, Ottman N, Belzer C, Huhtinen H, de Vos WM, Satokari R. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol. 2015;81(11):3655–3662. doi:.

    Not in our library10.1128/aem.04050-14 (opens in a new tab)

  15. 15.

    Ouwerkerk JP, Van Der Ark KCH, Davids M, Claassens NJ, Finestra TR, de Vos WM, Belzer C. Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl Environ Microbiol. 2016;82(23):6983–6993. doi:.

    Not in our library10.1128/aem.01641-16 (opens in a new tab)

  16. 16.

    Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol. 2008;74(5):1646–1648. doi:.

    Not in our library10.1128/aem.01226-07 (opens in a new tab)

  17. 17.

    Zhai Q, Feng S, Arjan N, Chen W. A next generation probiotic. Crit Rev Food Sci Nutr. 2019;59:3227–3236. doi:.

    Not in our library10.1080/10408398.2018.1517725 (opens in a new tab)

  18. 18.

    Ottman N, Davids M, Suarez-Diez M, Boeren S, Schaap PJ, Martins Dos Santos VAP,Smidt H, Belzer C, de Vos WM. Genome-scale model and omics analysis of metabolic capacities of reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol. 2017;83(18):e01014-17. doi:.

    Not in our library10.1128/aem.01014-17 (opens in a new tab)

  19. 19.

    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–9071. doi:.

    Not in our library10.1073/pnas.1219451110 (opens in a new tab)

  20. 20.

    Li J, Lin S, Vanhoutte PM, Woo CW, Xu A. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-/- mice. Circulation. 2016;133:2434–2446. doi:.

    Not in our library10.1161/circulationaha.115.019645 (opens in a new tab)

  21. 21.

    Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–113. doi:.

    Not in our library10.1038/nm.4236 (opens in a new tab)

  22. 22.

    Shin N-R, Lee J-C, Lee H-Y, Kim M-S, Whon TW, Lee M-S, Bae J-W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727–735. doi:.

    Not in our library10.1136/gutjnl-2012-303839 (opens in a new tab)

  23. 23.

    Shen J, Tong X, Sud N, Khound R, Song Y, Maldonado-Gomez MX, Walter J, Su Q. Low-Density lipoprotein receptor signaling mediates the triglyceride-lowering action of Akkermansia muciniphila in genetic-induced hyperlipidemia. Arterioscler Thromb Vasc Biol. 2016;36:1448–1456. doi:.

    Not in our library10.1161/atvbaha.116.307597 (opens in a new tab)

  24. 24.

    Zhao S, Liu W, Wang J, Shi J, Sun Y, Wang W, Ning G, Liu R, Hong J. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J Mol Endocrinol. 2017;58(1):1-14

    Not in our library10.1530/jme-16-0054 (opens in a new tab)

  25. 25.

    Gao X, Xie Q, Kong P, Liu L, Sun S, Xiong B, Huang B, Yan L, Sheng J, Xiang H. Polyphenol- and caffeine-rich postfermented Pu-erh tea improves diet-induced metabolic syndrome by remodeling intestinal homeostasis in mice. Infect Immun. 2018;86(1):e00601-17. doi:.

    Not in our library10.1128/iai.00601-17 (opens in a new tab)

  26. 26.

    Sheng L, Jena PK, Liu H-X, Hu Y, Nagar N, Bronner DN, Settles ML, Bäumler AJ, Wan Y-JY. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila. FASEB J. 2018;32(12):fj201800370R. doi:.

    Not in our library10.1096/fj.201800370r (opens in a new tab)

  27. 27.

    Lee H, Lee Y, Kim J, An J, Lee S, Kong H, Song Y, Lee C-K, Kim K. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes. 2018;9(2):155–165. doi:.

    Not in our library10.1080/19490976.2017.1405209 (opens in a new tab)

  28. 28.

    Hänninen A, Toivonen R, Pöysti S, Belzer C, Plovier H, Ouwerkerk JP, Emani R, Cani PD, De Vos WM. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut. 2018;67(8):1445–1453. doi:.

    Not in our library10.1136/gutjnl-2017-314508 (opens in a new tab)

  29. 29.
    Akkermansia muciniphila-Derived Extracellular Vesicles as a Mucosal Delivery Vector for Amelioration of Obesity in Mice · 2019
    No notice
  30. 30.
    Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis · 2019
    No notice
  31. 31.
    Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1−/Δ7 mice · 2019
    No notice
  32. 32.
    Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice · 2020
    No notice
  33. 33.

    Huo Y, Lu X, Wang X, Wang X, Chen L, Guo H, Zhang M, Li Y. Bifidobacterium animalis subsp. lactis A6 alleviates obesity associated with promoting mitochondrial biogenesis and function of adipose tissue in mice. Molecules. 2020;25(7):1490. doi:.

    Not in our library10.3390/molecules25071490 (opens in a new tab)

  34. 34.

    Kim S, Lee Y, Kim Y, Seo Y, Lee H, Ha J, Lee J, Choi Y, Oh H, Yoon Y, et al. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl Environ Microbiol. 2020;86(7):e03004-19

    Not in our library10.1128/aem.03004-19 (opens in a new tab)

  35. 35.

    Katiraei S, De Vries MR, Costain AH, Thiem K, Hoving LR, van Diepen JA, Smits HH, Bouter KE, Rensen PCN, Quax PHA, et al. Akkermansia muciniphila exerts lipid-lowering and immunomodulatory effects without affecting neointima formation in hyperlipidemic APOE*3-Leiden.CETP mice. Mol Nutr Food Res. 2020;64(15):e1900732. doi:.

    Not in our library10.1002/mnfr.201900732 (opens in a new tab)

  36. 36.

    Yoon HS, Cho CH, Yun MS, Jang SJ, You HJ, Kim J-H, Han D, Cha KH, Moon SH, Lee K, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021;6(5):563–573. doi:.

    Not in our library10.1038/s41564-021-00880-5 (opens in a new tab)

  37. 37.

    Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25:1096–1103. doi:.

    Not in our library10.1038/s41591-019-0495-2 (opens in a new tab)

  38. 38.

    Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020;8(1):e001319. doi:.

    Not in our library10.1136/bmjdrc-2020-001319 (opens in a new tab)

  39. 39.

    Shin J, Noh J-R, Chang D-H, Kim Y-H, Kim MH, Lee ES, Cho S, Ku BJ, Rhee M-S, Kim B-C, et al. Elucidation of akkermansia muciniphila probiotic traits driven by mucin depletion. Front Microbiol. 2019;10:1137. doi:.

    Not in our library10.3389/fmicb.2019.01137 (opens in a new tab)

  40. 40.

    Bodogai M, O’Connell J, Kim K, Kim Y, Moritoh K, Chen C, Gusev F, Vaughan K, Shulzhenko N, Mattison JA, et al. Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells. Sci Transl Med. 2018;10(467):eaat4271. doi:.

    Not in our library10.1126/scitranslmed.aat4271 (opens in a new tab)

  41. 41.

    Chelakkot C, Choi Y, Kim D-K, Park HT, Ghim J, Kwon Y, Jeon J, Kim M-S, Jee Y-K, Gho YS, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med. 2018;50(2):e450. doi:.

    Not in our library10.1038/emm.2017.282 (opens in a new tab)

  42. 42.

    Deng L, Ou Z, Huang D, Li C, Lu Z, Liu W, Wu F, Nong C, Gao J, Peng Y, et al. Diverse effects of different Akkermansia muciniphila genotypes on brown adipose tissue inflammation and whitening in a high-fat-diet murine model. Microb Pathog. 2020;147:104353. doi:.

    Not in our library10.1016/j.micpath.2020.104353 (opens in a new tab)

  43. 43.

    Okeke F, Roland BC, Mullin GE. The role of the gut microbiome in the pathogenesis and treatment of obesity. Glob Adv Health Med. 2014;3:44–57. doi:.

    Not in our library10.7453/gahmj.2014.018 (opens in a new tab)

  44. 44.

    Aguirre M, Venema K. The art of targeting gut microbiota for tackling human obesity. Genes Nutr. 2015;10:472. doi:.

    Not in our library10.1007/s12263-015-0472-4 (opens in a new tab)

  45. 45.

    Delzenne NM, Neyrinck AM, Bäckhed F, Cani PD. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011;7:639–646. doi:.

    Not in our library10.1038/nrendo.2011.126 (opens in a new tab)

  46. 46.

    Cani PD. Targeting gut microbiota with a complex mix of dietary fibers improves metabolic diseases. Kidney Int. 2019;95:14–16. doi:.

    Not in our library10.1016/j.kint.2018.11.012 (opens in a new tab)

  47. 47.

    Hussain A, Yadav MK, Bose S, Wang J-H, Lim D, Song Y-K, Ko S-G, Kim H. Daesiho-Tang is an effective herbal formulation in attenuation of obesity in mice through alteration of gene expression and modulation of intestinal microbiota. PLoS One. 2016;11(11):e0165483. doi:.

    Not in our library10.1371/journal.pone.0165483 (opens in a new tab)

  48. 48.

    Lee J, Jang J-Y, Kwon M-S, Lim SK, Kim N, Lee J, Park HK, Yun M, Shin M-Y, Jo HE, et al. Mixture of two lactobacillus plantarum strains modulates the gut microbiota structure and regulatory T cell response in diet-induced obese mice. Mol Nutr Food Res. 2018;62(24):e1800329. doi:.

    Not in our library10.1002/mnfr.201800329 (opens in a new tab)

  49. 49.
    Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice · 2018
    No notice
  50. 50.

    Wang L, Wu Y, Zhuang L, Chen X, Min H, Song S, Liang Q, Li A-D, Gao Q. Puerarin prevents high-fat diet-induced obesity by enriching Akkermansia muciniphila in the gut microbiota of mice. PLoS One. 2019;14(6):e0218490. doi:.

    Not in our library10.1371/journal.pone.0218490 (opens in a new tab)

  51. 51.

    Yang Y, Zhong Z, Wang B, Xia X, Yao W, Huang L, Wang Y, Ding W. Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology. 2019;44(12):2054–2064. doi:.

    Not in our library10.1038/s41386-019-0437-1 (opens in a new tab)

  52. 52.

    Wang J-H, Bose S, Kim H-G, Han K-S, Kim H. Fermented rhizoma atractylodis macrocephalae alleviates high fat diet-induced obesity in association with regulation of intestinal permeability and microbiota in rats. Sci Rep. 2015;5(1):8391. doi:.

    Not in our library10.1038/srep08391 (opens in a new tab)

  53. 53.

    Anhê FF, Nachbar RT, Varin TV, Trottier J, Dudonné S, Le Barz M, Feutry P, Pilon G, Barbier O, Desjardins Y, et al. Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice. Gut. 2019;68(3):453–464. doi:.

    Not in our library10.1136/gutjnl-2017-315565 (opens in a new tab)

  54. 54.

    Arias L, Goig GA, Cardona P, Torres-Puente M, Díaz J, Rosales Y, Garcia E, Tapia G, Comas I, Vilaplana C, et al. Influence of gut microbiota on progression to tuberculosis generated by high fat diet-induced obesity in C3HeB/FeJ mice. Front Immunol. 2019;10:2464. doi:.

    Not in our library10.3389/fimmu.2019.02464 (opens in a new tab)

  55. 55.

    Carmody RN, Gerber GK, Luevano JM, Gatti DM, Somes L, Svenson KL, Turnbaugh P. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2015;17(1):72–84. doi:.

    Not in our library10.1016/j.chom.2014.11.010 (opens in a new tab)

  56. 56.
    The gut microbiota of Colombians differs from that of Americans, Europeans and Asians · 2014
    No notice
  57. 57.

    Ettehad Marvasti F, Moshiri A, Taghavi MS, Riazi S, Taati M, Sadati SF, Ghaheri A, Masoomi M, Vaziri F, Fateh A, et al. The first report of differences in gut microbiota composition between obese and normal weight Iranian subjects. Iran Biomed J. 2020;24(3):148–154. doi:.

    Not in our library10.29252/ibj.24.3.148 (opens in a new tab)

  58. 58.
    Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes · 2016
    No notice
  59. 59.

    Teixeira FS, Grześkowiak T, Salminen LM, Laitinen S, Bressan J, Gouveia Peluzio M. Faecal levels of bifidobacterium and clostridium coccoides but not plasma lipopolysaccharide are inversely related to insulin and HOMA index in women. Clin Nutr. 2013;32:1017–1022. doi:.

    Not in our library10.1016/j.clnu.2013.02.008 (opens in a new tab)

  60. 60.

    Dao MC, Belda E, Prifti E, Everard A, Kayser BD, Bouillot J-L, Chevallier J-M, Pons N, Le Chatelier E, Ehrlich SD, et al. Akkermansia muciniphila abundance is lower in severe obesity, but its increased level after bariatric surgery is not associated with metabolic health improvement. Am J Physiol Endocrinol Metab. 2019;317(3):E446–E59. doi:.

    Not in our library10.1152/ajpendo.00140.2019 (opens in a new tab)

  61. 61.

    Santacruz A, Collado MC, García-Valdés L, Segura MT, Martín-Lagos JA, Anjos T, Martí-Romero M, Lopez RM, Florido J, Campoy C, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104(1):83–92. doi:.

    Not in our library10.1017/s0007114510000176 (opens in a new tab)

  62. 62.

    Karlsson CLJ, Onnerfält J, Xu J, Molin G, Ahrné S, Thorngren-Jerneck K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring). 2012;20(11):2257–2261. doi:.

    Not in our library10.1038/oby.2012.110 (opens in a new tab)

  63. 63.

    Liu R, Hong J, Xu X, Feng Q, Zhang D, Gu Y, Shi J, Zhao S, Liu W, Wang X, et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med. 2017;23(7):859–868. doi:.

    Not in our library10.1038/nm.4358 (opens in a new tab)

  64. 64.

    Borgo F, Verduci E, Riva A, Lassandro C, Riva E, Morace G, Borghi E. Relative abundance in bacterial and fungal gut microbes in obese children: a case control study. Child Obes. 2017;13:78–84. doi:.

    Not in our library10.1089/chi.2015.0194 (opens in a new tab)

  65. 65.

    Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, et al. Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe. 2019;26(2):252-264.e10. doi:.

    Not in our library10.1016/j.chom.2019.07.004 (opens in a new tab)

  66. 66.

    Salah M, Azab M, Ramadan A, Hanora A. New insights on obesity and diabetes from gut microbiome alterations in egyptian adults. OMICS. 2019;23:477–485. doi:.

    Not in our library10.1089/omi.2019.0063 (opens in a new tab)

  67. 67.

    Mitsou EK, Detopoulou M, Kakali A, Fragopoulou E, Nomikos T, Antonopoulou S, Panagiotakos DB, Kyriacou A. Mining possible associations of faecal A. muciniphila colonisation patterns with host adiposity and cardiometabolic markers in an adult population. Benef Microbes. 2019;10(7):741–749. doi:.

    Not in our library10.3920/bm2019.0033 (opens in a new tab)

  68. 68.

    Nistal E, Sáenz de Miera LE, Ballesteros PM, Sánchez-Campos S, García-Mediavilla MV, Álvarez-Cuenllas B, Linares P, Olcoz JL, Arias Loste MT, García Lobo JM, et al. An altered fecal microbiota profile in patients with non-alcoholic fatty liver disease (NAFLD) associated with obesity. Rev Esp Enferm Dig. 2019;111:275–282. doi:.

    Not in our library10.17235/reed.2019.6068/2018 (opens in a new tab)

  69. 69.

    de la Cuesta-Zuluaga J, Corrales-Agudelo V, Carmona JA, Abad JM, Escobar JS. Body size phenotypes comprehensively assess cardiometabolic risk and refine the association between obesity and gut microbiota. Int J Obes (Lond). 2018;42:424–432. doi:.

    Not in our library10.1038/ijo.2017.281 (opens in a new tab)

  70. 70.

    Liang C, Guo M, Liu T, Zhou X, Gong P, Lyu L, Niu H, Wu Y, Chen S, Han X, et al. Profiles of gut microbiota in children with obesity from Harbin, China and screening of strains with anti-obesity ability in vitro and in vivo. J Appl Microbiol. 2020;129(3):728–737. doi:.

    Not in our library10.1111/jam.14639 (opens in a new tab)

  71. 71.
    Genetic and environmental control of host-gut microbiota interactions · 2015
    No notice
  72. 72.

    Wu F, Guo X, Zhang M, Ou Z, Wu D, Deng L, Lu Z, Zhang J, Deng G, Chen S, et al. An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice. Anaerobe. 2020;61:102138. doi:.

    Not in our library10.1016/j.anaerobe.2019.102138 (opens in a new tab)

  73. 73.
    Genetics of Type 2 Diabetes—Pitfalls and Possibilities · 2015
    No notice
  74. 74.

    Tuomi T, Nagorny CLF, Singh P, Bennet H, Yu Q, Alenkvist I, Isomaa B, Östman B, Söderström J, Pesonen A-K, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23(6):1067–1077. doi:.

    Not in our library10.1016/j.cmet.2016.04.009 (opens in a new tab)

  75. 75.

    Huang T, Qi Q, Zheng Y, Ley SH, Manson JE, Hu FB, Qi L. Genetic predisposition to central obesity and risk of type 2 diabetes: two independent cohort studies. Diabetes Care. 2015;38(7):1306–1311. doi:.

    Not in our library10.2337/dc14-3084 (opens in a new tab)

  76. 76.

    Barrès R, Zierath JR. The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat Rev Endocrinol. 2016;12:441–451. doi:.

    Not in our library10.1038/nrendo.2016.87 (opens in a new tab)

  77. 77.
    Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance · 2013
    No notice
  78. 78.

    Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD, Levenez F, Chilloux J, Hoyles L, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65(3):426–436. doi:.

    Not in our library10.1136/gutjnl-2014-308778 (opens in a new tab)

  79. 79.

    Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Mannerås-Holm L, Ståhlman M, Olsson LM, Serino M, Planas-Fèlix M, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017;23(7):850–858. doi:.

    Not in our library10.1038/nm.4345 (opens in a new tab)

  80. 80.

    de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, Velásquez-Mejía EP, Carmona JA, Abad JM, Escobar JS. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care. 2017;40:54–62. doi:.

    Not in our library10.2337/dc16-1324 (opens in a new tab)

  81. 81.

    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després J-P, Fullerton HJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–360. doi:.

    Not in our library10.1161/cir.0000000000000350 (opens in a new tab)

  82. 82.
    Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019 · 2020
    Corrected
  83. 83.

    Peng J, Xiao X, Hu M, Zhang X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 2018;214:153–157. doi:.

    Not in our library10.1016/j.lfs.2018.10.063 (opens in a new tab)

  84. 84.

    Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120:1183–1196. doi:.

    Not in our library10.1161/circresaha.117.309715 (opens in a new tab)

  85. 85.

    Al-Waiz M, Mikov M, Mitchell SC, Smith RL. The exogenous origin of trimethylamine in the mouse. Metabolism. 1992;41:135–136. doi:.

    Not in our library10.1016/0026-0495(92)90140-6 (opens in a new tab)

  86. 86.

    Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr. 1998;18:39–61. doi:.

    Not in our library10.1146/annurev.nutr.18.1.39 (opens in a new tab)

  87. 87.

    Zeisel SH, Wishnok JS, Blusztajn JK. Formation of methylamines from ingested choline and lecithin. J Pharmacol Exp Ther. 1983;225:320–324.

    Not in our library

  88. 88.

    Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013;17:49–60. doi:.

    Not in our library10.1016/j.cmet.2012.12.011 (opens in a new tab)

  89. 89.

    Zhu W, Buffa JA, Wang Z, Warrier M, Schugar R, Shih DM, Gupta N, Gregory JC, Org E, Fu X, et al. Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N-oxide-generating pathway, modulates platelet responsiveness and thrombosis risk. J Thromb Haemost. 2018;16(9):1857–1872. doi:.

    Not in our library10.1111/jth.14234 (opens in a new tab)

  90. 90.

    Treacy EP, Akerman BR, Chow LM, Youil R, Bibeau C, Lin J, Bruce AG, Knight M, Danks DM, Cashman JR, et al. Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication. Hum Mol Genet. 1998;7:839–845. doi:.

    Not in our library10.1093/hmg/7.5.839 (opens in a new tab)

  91. 91.

    Ettinger G, MacDonald K, Reid G, Burton JP. The influence of the human microbiome and probiotics on cardiovascular health. Gut Microbes. 2014;5:719–728. doi:.

    Not in our library10.4161/19490976.2014.983775 (opens in a new tab)

  92. 92.

    Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63. doi:.

    Not in our library10.1038/nature09922 (opens in a new tab)

  93. 93.

    Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:2089–2105. doi:.

    Not in our library10.1016/j.jacc.2019.03.024 (opens in a new tab)

  94. 94.

    Ahmadmehrabi S, Tang WHW. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32:761–766. doi:.

    Not in our library10.1097/hco.0000000000000445 (opens in a new tab)

  95. 95.
    The Role of Gut Microbiota in Atherosclerosis and Hypertension · 2018
    No notice
  96. 96.
    Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health · 2018
    No notice
  97. 97.

    Moreira GV, Azevedo FF, Ribeiro LM, Santos A, Guadagnini D, Gama P, Liberti EA, Saad M, Carvalho C. Liraglutide modulates gut microbiota and reduces NAFLD in obese mice. J Nutr Biochem. 2018;62:143–154. doi:.

    Not in our library10.1016/j.jnutbio.2018.07.009 (opens in a new tab)

  98. 98.

    Wang H, Wang L, Li Y, Luo S, Ye J, Lu Z, Li X, Lu H. The HIF-2α/PPARα pathway is essential for liraglutide-alleviated, lipid-induced hepatic steatosis. Biomed Pharmacother = Biomedecine Pharmacotherapie. 2021;140:111778. doi:.

    Not in our library10.1016/j.biopha.2021.111778 (opens in a new tab)

  99. 99.
    Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury in a Mouse Model · 2017
    No notice
  100. 100.

    Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 2012;95:50–60. doi:.

    Not in our library10.5740/jaoacint.sge_macfarlane (opens in a new tab)

  101. 101.

    Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M. Free fatty acid receptors in health and disease. Physiol Rev. 2020;100:171–210. doi:.

    Not in our library10.1152/physrev.00041.2018 (opens in a new tab)

  102. 102.

    Yu C, Liu S, Chen L, Shen J, Niu Y, Wang T, Zhang W, Fu L. Effect of exercise and butyrate supplementation on microbiota composition and lipid metabolism. J Endocrinol. 2019;243(2):125–135. doi:.

    Not in our library10.1530/joe-19-0122 (opens in a new tab)

  103. 103.

    Le Poul E, Loison C, Struyf S, Springael J-Y, Lannoy V, Decobecq M-E, Brezillon S, Dupriez V, Vassart G, Van Damme J, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278(28):25481–25489. doi:.

    Not in our library10.1074/jbc.m301403200 (opens in a new tab)

  104. 104.

    Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105(43):16767–16772. doi:.

    Not in our library10.1073/pnas.0808567105 (opens in a new tab)

  105. 105.

    Christiansen CB, Gabe MBN, Svendsen B, Dragsted LO, Rosenkilde MM, Holst JJ. The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am J Physiol Gastrointest Liver Physiol. 2018;315(1):G53–G65. doi:.

    Not in our library10.1152/ajpgi.00346.2017 (opens in a new tab)

  106. 106.
    The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents · 2014
    No notice
  107. 107.
    Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression · 2018
    No notice
  108. 108.

    Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Ghrelin GN. CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev. 2017;97:411–463. doi:.

    Not in our library10.1152/physrev.00031.2014 (opens in a new tab)

  109. 109.

    Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):728–742. doi:.

    Not in our library10.1038/nrendo.2012.140 (opens in a new tab)

  110. 110.
    The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism · 2014
    No notice
  111. 111.

    Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005;82:559–567. doi:.

    Not in our library10.1093/ajcn.82.3.559 (opens in a new tab)

  112. 112.

    Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4(1):1829. doi:.

    Not in our library10.1038/ncomms2852 (opens in a new tab)

  113. 113.

    De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156(1–2):84–96. doi:.

    Not in our library10.1016/j.cell.2013.12.016 (opens in a new tab)

  114. 114.
    Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids · 2014
    Not checked
  115. 115.
    Microbial Metabolic Networks at the Mucus Layer Lead to Diet-Independent Butyrate and Vitamin B 12 Production by Intestinal Symbionts · 2017
    No notice
  116. 116.

    Chia LW, Hornung BVH, Aalvink S, Schaap PJ, de Vos WM, Knol J, Belzer C. Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal anaerostipes caccae using a metatranscriptomic approach. Antonie Van Leeuwenhoek. 2018;111(6):859–873. doi:.

    Not in our library10.1007/s10482-018-1040-x (opens in a new tab)

  117. 117.

    Belzer C, de Vos WM. Microbes inside–from diversity to function: the case of Akkermansia. ISME J. 2012;6:1449–1458. doi:.

    Not in our library10.1038/ismej.2012.6 (opens in a new tab)

  118. 118.

    Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman S. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13(5):517–526. doi:.

    Not in our library10.1016/j.cmet.2011.02.018 (opens in a new tab)

  119. 119.

    Roshanravan N, Mahdavi R, Alizadeh E, Jafarabadi MA, Hedayati M, Ghavami A, Alipour S, Alamdari N, Barati M, Ostadrahimi A, et al. Effect of butyrate and inulin supplementation on glycemic status, lipid profile and glucagon-like peptide 1 level in patients with type 2 diabetes: a randomized double-blind, placebo-controlled trial. Horm Metab Res. 2017;49(11):886–891. doi:.

    Not in our library10.1055/s-0043-119089 (opens in a new tab)

  120. 120.

    Moran BM, Flatt PR, McKillop AM. G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homoeostasis. Acta Diabetol. 2016;53(2):177–188. doi:.

    Not in our library10.1007/s00592-015-0826-9 (opens in a new tab)

  121. 121.
    Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation · 2018
    No notice
  122. 122.

    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470–1481. doi:.

    Not in our library10.2337/db07-1403 (opens in a new tab)

  123. 123.

    Frazier TH, DiBaise JK, McClain CJ. Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. JPEN J Parenter Enteral Nutr. 2011;35(5_suppl):14S–20S. doi:.

    Not in our library10.1177/0148607111413772 (opens in a new tab)

  124. 124.
    Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability · 2009
    No notice
  125. 125.

    Bastard J-P, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4-12.

    Not in our library

  126. 126.

    Grander C, Adolph TE, Wieser V, Lowe P, Wrzosek L, Gyongyosi B, Ward DV, Grabherr F, Gerner RR, Pfister A, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018;67(5):891–901. doi:.

    Not in our library10.1136/gutjnl-2016-313432 (opens in a new tab)

  127. 127.

    Gonzalez A, Krieg R, Massey HD, Carl D, Ghosh S, Gehr TWB, Ghosh SS. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant. 2019;34(5):783–794. doi:.

    Not in our library10.1093/ndt/gfy238 (opens in a new tab)

  128. 128.

    Cheng D, Xu J-H, Li J-Y, Wang S-Y, Wu T-F, Chen Q-K, Yu T. Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner. Exp Cell Res. 2018;368(1):101–110. doi:.

    Not in our library10.1016/j.yexcr.2018.04.018 (opens in a new tab)

  129. 129.
    Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function · 2017
    No notice
  130. 130.

    Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA, Florin THJ. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105(11):2420–2428. doi:.

    Not in our library10.1038/ajg.2010.281 (opens in a new tab)

  131. 131.

    Vigsnæs LK, Brynskov J, Steenholdt C, Wilcks A, Licht TR. Gram-negative bacteria account for main differences between faecal microbiota from patients with ulcerative colitis and healthy controls. Benef Microbes. 2012;3:287–297. doi:.

    Not in our library10.3920/bm2012.0018 (opens in a new tab)

  132. 132.
    Extracellular Vesicles Derived from Gut Microbiota, Especially Akkermansia muciniphila, Protect the Progression of Dextran Sulfate Sodium-Induced Colitis · 2013
    No notice
  133. 133.
    Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice · 2019
    No notice
  134. 134.
    Strain-Specific Anti-inflammatory Properties of Two Akkermansia muciniphila Strains on Chronic Colitis in Mice · 2019
    No notice
  135. 135.

    Wang L, Tang L, Feng Y, Zhao S, Han M, Zhang C, Yuan G, Zhu J, Cao S, Wu Q, et al. A purified membrane protein from akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8 + T cells in mice. Gut. 2020;69:1988–1997. doi:.

    Not in our library10.1136/gutjnl-2019-320105 (opens in a new tab)

  136. 136.

    Seregin SS, Golovchenko N, Schaf B, Chen J, Pudlo NA, Mitchell J, Baxter NT, Zhao L, Schloss PD, Martens EC et al. NLRP6 protects Il10 Mice from colitis by limiting colonization of Akkermansia muciniphila. Cell Rep. 2017;19:733–745. doi:.

    Not in our library10.1016/j.celrep.2017.03.080 (opens in a new tab)

  137. 137.

    Ottman N, Huuskonen L, Reunanen J, Boeren S, Klievink J, Smidt H, Belzer C, de Vos WM. Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front Microbiol. 2016;7:1157. doi:.

    Not in our library10.3389/fmicb.2016.01157 (opens in a new tab)

  138. 138.

    Zhang L, Qin Q, Liu M, Zhang X, He F, Wang G. Akkermansia muciniphila can reduce the damage of gluco/lipotoxicity, oxidative stress and inflammation, and normalize intestine microbiota in streptozotocin-induced diabetic rats. Pathog Dis. 2018;76(4). doi:.

    Not in our library10.1093/femspd/fty028 (opens in a new tab)

  139. 139.

    Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010;6(1):392. doi:.

    Not in our library10.1038/msb.2010.46 (opens in a new tab)

  140. 140.

    Meng X, Wang W, Lan T, Yang W, Yu D, Fang X, Wu H. A purified aspartic protease from plays an important role in degrading Muc2. Int J Mol Sci. 2019;21(1):72. doi:.

    Not in our library10.3390/ijms21010072 (opens in a new tab)

  141. 141.

    Meng X, Zhang J, Wu H, Yu D, Fang X. Aspartic protease Amuc_1434* inhibits human colorectal cancer LS174T cell viability via TRAIL-mediated apoptosis pathway. Int J Mol Sci. 2020:21(9):3385. doi:.

    Not in our library10.3390/ijms21093385 (opens in a new tab)

  142. 142.

    Kosciow K, Deppenmeier U. Characterization of a phospholipid-regulated β-galactosidase from Akkermansia muciniphila involved in mucin degradation. MicrobiologyOpen. 2019;8(8):e00796. doi:.

    Not in our library10.1002/mbo3.796 (opens in a new tab)

  143. 143.

    Kosciow K, Deppenmeier U. Characterization of three novel β-galactosidases from Akkermansia muciniphila involved in mucin degradation. Int J Biol Macromol. 2020;149:331–340. doi:.

    Not in our library10.1016/j.ijbiomac.2020.01.246 (opens in a new tab)

  144. 144.

    Kuipers ME, Hokke CH, Smits HH, Nolte-’t Hoen ENM. Pathogen-derived extracellular vesicle-associated molecules that affect the host immune system: an overview. Front Microbiol. 2018;9:2182. doi:.

    Not in our library10.3389/fmicb.2018.02182 (opens in a new tab)

  145. 145.
    Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development · 2019
    No notice
  146. 146.

    Cani PD, Knauf C. A newly identified protein from Akkermansia muciniphila stimulates GLP-1 secretion. Cell Metab. 2021;33(6):1073–1075. doi:.

    Not in our library10.1016/j.cmet.2021.05.004 (opens in a new tab)

  147. 147.

    Everard A, Lazarevic V, Gaïa N, Johansson M, Ståhlman M, Backhed F, Delzenne NM, Schrenzel J, François P, Cani PD, et al. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 2014;8(10):2116–2130. doi:.

    Not in our library10.1038/ismej.2014.45 (opens in a new tab)

  148. 148.
    Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice · 2015
    No notice
  149. 149.
    Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity · 2017
    No notice
  150. 150.

    Villamil SI, Huerlimann R, Morianos C, Sarnyai Z, Maes GE. Adverse effect of early-life high-fat/high-carbohydrate (“Western”) diet on bacterial community in the distal bowel of mice. Nutr Res (New York, NY). 2018;50:25–36. doi:.

    Not in our library10.1016/j.nutres.2017.11.008 (opens in a new tab)

  151. 151.

    Fujisaka S, Usui I, Nawaz A, Igarashi Y, Okabe K, Furusawa Y, Watanabe S, Yamamoto S, Sasahara M, Watanabe Y, et al. Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity. Sci Rep. 2020;10(1):5544. doi:.

    Not in our library10.1038/s41598-020-62506-w (opens in a new tab)

  152. 152.

    Régnier M, Rastelli M, Morissette A, Suriano F, Le Roy T, Pilon G, Delzenne NM, Marette A, Van Hul M, Cani PD. Rhubarb supplementation prevents diet-induced obesity and diabetes in association with increased in mice. Nutrients. 2020;12(10):2932. doi:.

    Not in our library10.3390/nu12102932 (opens in a new tab)

  153. 153.

    Wu T, Gao Y, Hao J, Geng J, Zhang J, Yin J, Liu R, Sui W, Gong L, Zhang M, et al. Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice. Food Res Int. 2020;128:108774. doi:.

    Not in our library10.1016/j.foodres.2019.108774 (opens in a new tab)

  154. 154.
    The physico-chemical properties of dietary fibre determine metabolic responses, short-chain Fatty Acid profiles and gut microbiota composition in rats fed low- and high-fat diets. · 2015
    Not checked
  155. 155.

    Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto J-M, Kennedy S, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–546. doi:.

    Not in our library10.1038/nature12506 (opens in a new tab)

  156. 156.

    Remely M, Tesar I, Hippe B, Gnauer S, Rust P, Haslberger AG. Gut microbiota composition correlates with changes in body fat content due to weight loss. Benef Microbes. 2015;6(4):431–439. doi:.

    Not in our library10.3920/bm2014.0104 (opens in a new tab)

  157. 157.
    Specific gut microbiota features and metabolic markers in postmenopausal women with obesity · 2015
    No notice
  158. 158.

    Wang Z, Saha S, Van Horn S, Thomas E, Traini C, Sathe G, Rajpal DK, Brown JR. Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects. Endocrinol Diabetes Metab. 2018;1(1):e00009. doi:.

    Not in our library10.1002/edm2.9 (opens in a new tab)

  159. 159.
    Gut microbiota dysbiosis contributes to the development of hypertension · 2017
    No notice
  160. 160.

    Singh H, Torralba MG, Moncera KJ, DiLello L, Petrini J, Nelson KE, Pieper R. Gastro-intestinal and oral microbiome signatures associated with healthy aging. Geroscience. 2019;41(6):907–921. doi:.

    Not in our library10.1007/s11357-019-00098-8 (opens in a new tab)

  161. 161.

    Medina-Vera I, Sanchez-Tapia M, Noriega-López L, Granados-Portillo O, Guevara-Cruz M, Flores-López A, Avila-Nava A, Fernández ML, Tovar AR, Torres N, et al. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019;45:122–131. doi:.

    Not in our library10.1016/j.diabet.2018.09.004 (opens in a new tab)

  162. 162.

    Journey EK, Ortega-Santos CP, Bruening M, Whisner CM. Changes in weight status and the intestinal microbiota among college freshman, aged 18 years. J Adolesc Health. 2020;66(2):166–171. doi:.

    Not in our library10.1016/j.jadohealth.2019.06.005 (opens in a new tab)

  163. 163.

    Hsu C-N, Chang-Chien G-P, Lin S, Hou C-Y, Lu P-C, Tain Y-L. Association of trimethylamine, trimethylamine N-oxide, and dimethylamine with cardiovascular risk in children with chronic kidney disease. J Clin Med. 2020:9(2):336. doi:.

    Not in our library10.3390/jcm9020336 (opens in a new tab)

  164. 164.

    Kim B-S, Song M-Y, Kim H. The anti-obesity effect of ephedra sinica through modulation of gut microbiota in obese Korean women. J Ethnopharmacol. 2014;152(3):532–539. doi:.

    Not in our library10.1016/j.jep.2014.01.038 (opens in a new tab)

  165. 165.
    Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota · 2016
    No notice
  166. 166.

    Payahoo L, Khajebishak Y, Alivand MR, Soleimanzade H, Alipour S, Barzegari A, Ostadrahimi A. Investigation the effect of oleoylethanolamide supplementation on the abundance of Akkermansia muciniphila bacterium and the dietary intakes in people with obesity: a randomized clinical trial. Appetite. 2019;141:104301. doi:.

    Not in our library10.1016/j.appet.2019.05.032 (opens in a new tab)

  167. 167.
    Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial · 2018
    No notice
  168. 168.

    Zhang L, Ouyang Y, Li H, Shen L, Ni Y, Fang Q, Wu G, Qian L, Xiao Y, Zhang J, et al. Metabolic phenotypes and the gut microbiota in response to dietary resistant starch type 2 in normal-weight subjects: a randomized crossover trial. Sci Rep. 2019;9(1):4736. doi:.

    Not in our library10.1038/s41598-018-38216-9 (opens in a new tab)

  169. 169.

    Dong TS, Luu K, Lagishetty V, Sedighian F, Woo S-L, Dreskin BW, Katzka W, Chang C, Zhou Y, Arias-Jayo N, et al. A high protein calorie restriction diet alters the gut microbiome in obesity. Nutrients. 2020;12(10):3221. doi:.

    Not in our library10.3390/nu12103221 (opens in a new tab)

  170. 170.

    Cortez RV, Petry T, Caravatto P, Pessôa R, Sanabani SS, Martinez MB, Sarian T, Salles JE, Cohen R, Taddei CR, et al. Shifts in intestinal microbiota after duodenal exclusion favor glycemic control and weight loss: a randomized controlled trial. Surg Obes Relat Dis. 2018;14(11):1748–1754. doi:.

    Not in our library10.1016/j.soard.2018.07.021 (opens in a new tab)

  171. 171.
    Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome · 2019
    Not checked
  172. 172.

    Shin NR, Gu N, Choi HS, Kim H. Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation. Am J Physiol Endocrinol Metab. 2020;318(1):E52–E61. doi:.

    Not in our library10.1152/ajpendo.00221.2019 (opens in a new tab)

Questions about this paper

We email you if it is retracted, withdrawn, corrected or flagged.

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.