Fatty Acid Diets: Regulation of Gut Microbiota Composition and Obesity and Its Related Metabolic Dysbiosis

1Fatty acids (FAs) are the principal components of triacylglycerols found in oils and fats, which are the second primary source of dietary energy for humans. Several FAs are obtained from different types of foodstuff and can be affected during their processing, storage, and cooking and various eating habits. The majority of FAs dietary intake (>95%) is available to the bloodstream through efficient processes of digestion and absorption.

2FAs furnish energy (9 kcal per gram corresponding to 20%–35% of total calorie intake in adults); carry fat-soluble vitamins (A, D, E, and K); constitute the cell-membrane phospholipids; and act on its fluidity and signaling, immune system regulation, blood clots, and cholesterol metabolism.

3On the other hand, fat production and accumulation in the body can be related to calories furnished by unbalanced FA intake and expended quantities, related to a lack of physical activities, genetic predisposition, and pathways involving metabolites and hormones.

4Furthermore, these dysfunctions can be associated with unbalanced microbiota composition in the host gut, which is the complex tract through which food passes during a lifetime and has found an abundant and dynamic population of microbiota. Thus, the gut is home to about 100 trillion organisms, with 35,000 species of bacteria, of which small the intestine presents 107–108 and the large intestine presents 1010–1011 cells per mL of contents. This microbiota compound is mainly anaerobic, in which 98% is constituted by phyla Bacteroidetes (9%–42%) (Porpyromonas and Prevotella), Firmicutes (30–52%) (Ruminococcus, Clostridium, and Eubacteria) and Actinobacteria (1–13%) (Bifidobacterium) and in which 2% is constituted by phylum Lactobacillae (2%) (Streptococci (2%) and Enterobacteria (1%)). The most crucial gut microbiota activity is involved with short-chain fatty acids (SCFAs), produced by fermentation, which is represented by Ruminococcaceae and Eubacterium in the order Clostridia, classes Clostridia and Firmicutes, from prebiotics: polysaccharides (resistant starches, hemicellulose, pectins, and gums), oligosaccharides, proteins, peptides, and glycoproteins. The SCFAs are a group that presents 1–6 saturated carbons in their structures. The most relevant SCFAs produced are acetate > propionate ≥ butyrate. Propionate is abundantly synthesized by Bacteroidetes and Negativicutes, utilizing succinate. Butyrate is broadly produced by Clostridial clusters IV, XIVa, and XVI (Firmicutes) through the butyrate kinase or butyryl-coenzyme A (CoA): acetate CoA-transferase pathways, and this last pathway provides a high quantity of acetate. The beneficial effects of the SCFAs produced by the gut microbiota are summarized in Figure 1.

5The SCFAs produced in the colon are immediately absorbed and furnish energy for colonocytes, and the remaining SCFAs are immediately incorporated into the hepatic portal vein by passive diffusion and active transport mechanisms and contribute to the optimal function of several organs. Therefore, studies have demonstrated that the energy furnished to the host from diet intake is associated with modulation of the gut microbiota composition and leads to SCFA production. Also, FA diet has contributed to health promotion and disease prevention, including obesity and its related disorders.

6Obesity represents a consequence of abnormal fat accumulation in the body, resulting in high energy, which may lead to a pro-inflammatory response, and culminating at several disorders, such as insulin resistance and inflammatory diseases.

7The objective of this review is to provide an overview of fatty acid intake and gut microbiota composition for host health promotion and obesity prevention and its related metabolic dysbioses (e.g., coronary heart diseases and type 2 diabetes mellitus) through the compilation of several scientific articles published in the last five years related to studies with animal models and human subjects.

8Medium-chain fatty acids (MCFAs) are a group that presents 7–12 saturated carbons in their structures. The most common MCFAs are caprylic (C8:0), capric (C10:0), and lauric (C12:0) acids. The common diet sources of caprylic, capric, and lauric acids are coconut, palm kernel, and human milk with 5–8%, 6–7%, and 48–58%, respectively. MCFA digestion and absorption occur in the stomach, catalyzed by lingual and gastric lipases, solubilized in the aqueous phase of the intestinal contents, absorbed bounded to albumin, and transported to the liver via the portal vein. These acids do not need carnitine shuttle to enter mitochondria; however, they increase the energy spent, regulate protein activation, reduce adiposity and preserve insulin action in muscle and fat, induce satiety, increase mucosal microvillus enzymes activity in the small intestine, elongate to long-chain fatty acids, and resynthesize triglycerides. MCFAs have shorter biological half-time and higher stability to lipoperoxidation. Considering the lack of scientific evidence that address human studies with MCFAs, the effects of MCFAs-rich diet consumption on gut microbiota on obesity and its related diseases that occur in animal model studies are summarized in Table 1.

9Several studies on MCFAs reported that the increase of Bacteroidetes and the decrease of Firmicutes and Proteobacteria in mice gut consequently lowered the inflammation and obesity effects. Furthermore, the increase of the Bacteroidetes to Firmicutes ratio as well as the abundance of Ruminococcaceae, Bifidobacterium, and Lactobacillus are associated with SCFA production. Moreover, these bacteria are correlated with reducing effects of obesity, inflammatory bowel disease (IBD), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD) in the hosts. Bifidobacterium and Lactobacillus are predominantly abundant in the human gut during early life, producing lactate and acetate acids protecting the hosts against enter-pathogenic agents. The natural sources of MCFAs are human milk (9–15%) and virgin coconut oil (61%), presenting higher composition compared with infant formula (8–42%).

10However, diets rich in coconut oil ≥25% administrated to healthy female animal models for 8 or 10 weeks showed obesity and its related dysfunction effects and increase of Allobaculum, Clostridium, Lactobacillus, Staphylococcus, and the Firmicutes to Bacteroidetes ratio in their guts.

11Long-chain fatty acids (LCFAs) are a group that presents 13–18 saturated carbons in their structures. The LCFAs in the diet are myristic (C14:0), palmitic (C16:0), and stearic (C18:0) acids. The primary dietary sources of myristic acid include human milk, palm olein, and coconut (8–20%). Palmitic acid (PA) is commonly found in olive, human milk, cottonseed, and palm olein (20–47%). Stearic acid occurs in pumpkin, sesame, and human milk (6–7%).

12Therefore, LCFAs represent 80–90% of total saturated fatty acid food intake, between 20–30 g per day corresponding to PA. However, PA intake (exogenous) is counterbalanced by PA endogenous biosynthesis via de novo lipogenesis (DNL), crucial to maintaining cell membrane fluidity and insulin sensitivity. In normal physiology conditions, PA accumulation is prevented by enhanced Δ-9 desaturation to palmitoleic acid (16:1 n-7) and/or elongation to stearic acid and/or Δ-9 desaturation to oleic (18:1 n-9) and then elongation to eicosenoic acid (20:1 n-9). The effects of LCFA-rich diet consumption on gut microbiota composition in animal models are summarized in Table 2.

13In general, the increase of the Bacteroidetes to Firmicutes ratio was due to low fatty acid diets (7% of energy), and high fatty acids (25% of energy) of LCFAs was reported for healthy men and women (21–65 years old). Additionally, the main genera recorded by several studies are represented by Blautia, Clostridium, Coprococcus, Dialister, Lachnospira, Lactococcus, Lachnobacterium, Phascolarctobacterium, Roseburia, Ruminococcus (Firmicutes), Bacteroides, Paraprevotella, Parabacteroides, and Prevotella (Bacteroidetes), correlated with SCFA production, obesity, and its related metabolic dysbiosis reduction.

14Additionally, another gut microbiota feature is related to the most abundant Firmicutes in the intestine of healthy subjects and followed by relatively increasing Bacteroidetes. This behavior is maintained by equilibrated amounts of energy intake and expenditure by the host, which play a key role to keep the symbiotic relationship between gut microbiota and host. Thus, this harmonic relationship between the host and gut microbiota can allow the increase of SCFA production (acetic, propionic and butyric acids) which are crucial to the homeostasis and diseases of the host.

15However, the increase of the Firmicutes to Bacteroidetes ratio, including Actinobacteria, was recorded with LCFA-rich diets (34–72% of energy) fed to healthy animal models. Additionally, increased effects of obesity, adipose tissue, plasma cholesterol, total cholesterol, weight gain, hypertension, insulin resistance, inflammatory bowel diseases (IBD), nonalcoholic steatohepatitis (NASH) in the studied subjects occurred. Obesity and its related metabolic syndromes are associated with increase of Desulfovibrio and Bilophila wadsworthia (Proteobacteria) and decrease of Bifidobacterium spp. (Actinobacteria).

16Therefore, higher caloric intake and lower energy expenditure by animal models and human subjects show increasing Firmicutes abilities for energy extraction from diet and SCFA (acetate and butyrate) production and consequently elevating mass weight gain of the host and obesity by fat accumulation in adipocyte tissue. Additionally, decreasing Bacteroidetes at 50% compared with the Firmicutes ratio, including the abundance of Actinobacteria and Proteobacteria, is correlated with obesity and its related metabolic dysbioses.

17Monounsaturated fatty acids (MUFAs) are an unsaturated group with one double bond in their structures. The MUFAs include palmitoleic (C16:1 n-7), oleic (C18:1 n-9), and eicosenoic (C20:1 n-9) acids. The MUFAs are endogenously obtained by Δ-9 desaturation, palmitoleic from palmitic acid and oleic from stearic acid, and by elongation of oleic to eicosenoic acid. The MUFAs are obtained through ingestion; oleic acid is the most representative with 25–71% in safflower, sesame, pumpkin seed, rice bran, human milk, rapeseed, olive, and peanut and with eicosenoic acid with 7–17% in wheat germ, rapeseed, and hemp.

18MUFA consumption is associated with reduced effects of obesity and its related metabolic syndromes. Furthermore, these health beneficial effects demonstrated by MUFAs result from their apolipoproteins (E and C-III) that present a high affinity for the hepatic receptors and rapidly activate synthetic and catabolic pathways for triacylglycerol-rich lipoprotein metabolism. Moreover, the consumption of MUFAs-rich diet showed positive health effects, e.g., extra virgin olive oil increased the gut microbiota diversity of healthy and unhealthy animal models, including humans under risk of metabolic syndrome. Effects of MUFA-rich diet consumption on gut microbiota composition in animal models are summarized in Table 3.

19The increased Bacteroidetes to Firmicutes ratio, including Bifidobacterium spp. (Actinobacteria), was recorded for MUFA-rich diet (10–76% of energy) administrated to humans for several weeks (Table 4). The increase in Bacteroidetes and Bifidobacterium spp. is correlated with high SCFA (acetic, propionic and butyric acids) production. Among SCFAs, butyrate is the most important because it is an energy source for colonocytes and, on the other hand, triggers Firmicutes to reduce dietary energy harvest and consequently decreases adipose tissue fat accumulation in hosts.

20Consequently, MUFA-rich diet shows decreasing effects of obesity, weight gain, insulin resistance, hypertension, body mass index (BMI), and nonalcoholic steatohepatitis (NASH). SCFAs are crucial biomacromolecular substances utilized for the homeostasis and disease of the host, protecting or reducing the effects of obesity, diabetes, inflammatory bowel diseases (IBD) and cardiovascular diseases (CVD).

21The polyunsaturated fatty acids (PUFAs) are an unsaturated group that presents two or up to six double bonds in their structures. PUFAs are essential FAs (cannot be synthesized by human or higher animals’ bodies and are required from dietary intake) constituted by α-linolenic acid (ALA) from the n–3 PUFA family and by linoleic acid (LA) from the n–6 PUFA family. ALA is abundant in flaxseed (53 g), canola (18 g), and soybean oils (7 g). LA is found in soybean (56 g), corn (53 g), canola (19 g), flaxseed (14 g), and safflower oils (12.72 g).

22In the body, ALA is converted to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) through a series of desaturation and elongation reactions and presents effects of anti-inflammation, vasodilation, bronchodilation, and anti-platelet aggregation, and LA follows the same pathways, shares the same enzymes, competes with ALA for its desaturation and elongation processes, is converted to arachidonic acid (ARA), and presents an antagonistic effect to ALA and pathophysiology.

23Furthermore, an n–3 PUFA-rich diet is correlated with decreasing or preventing adipose tissue fat accumulation, insulin resistance, inflammation, hypertension, atherosclerosis, obesity, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). In contrast, an n–6 PUFA-rich dietary intake is associated with metabolic dysbioses such as obesity, inflammatory bowel diseases (IBD), nonalcoholic steatohepatitis (NASH), and CVD. Due to competition and antagonistic effects of n–6 against n–3 PUFAs, the recommended balanced dietary ratio of n–6/n–3 intake is 1/1 or 2/1–10/1.

24Thus, dietary PUFAs play a crucial role in a host specific to gut microbiota composition and in the ability of the production of MUFA-derived metabolites. Also, n–3 PUFA intake is related to the abundance of gut microbiota composition and to increasing SCFA production. Effects of PUFA-rich diet consumption on gut microbiota composition in animal models are summarized in Table 5.

25The increased Bacteroidetes to Firmicutes ratio, including Actinobacteria and Proteobacteria, was reported with administration of n–3 PUFAs in a low fat-diet or high-fat diet and of n–6/n–3 PUFA proportions (1/2 or 3/1–11/1) to humans (Table 6). The results demonstrated the decreased effects of obesity, inflammation, weight gain, nonalcoholic steatohepatitis (NASH), and type 2 diabetes mellitus (T2DM). Furthermore, the abundance of the Bacteroidetes to Firmicutes ratio is correlated with increasing SCFA (acetate, propionate, and butyrate acids) production. Butyrate is a substrate for colonocytes, and all SCFAs produced are important to biomacromolecular substances linked to homeostasis and disease of the host.

26However, interestingly, lowering obesity effects were recorded for healthy female genetically modified mice compared with wild-type mice; administrating safflower oil (n–6 PUFA-rich diet) for 21 weeks increased Bacteroidetes to Firmicutes ratio, including Proteobacteria. Inversely, weight gain remained stable with decreased Helicobacter and Clostridiales in healthy mice (male and female) given n–3 PUFA of fish oil (40% EPA- and 27% DHA-rich diet) for two weeks. Helicobacter and Clostridiales are related to increasing effects of insulin resistance, low-density lipoprotein-cholesterol (LDL-C), IBD, NASH, T2DM, and CVD.

27With regard to diets, n–6/n–3 PUFA proportion at 1/2 demonstrated anti-inflammatory effects on pups with increased Blautia (Firmicutes) and decreased Bacteroidetes. Blautia is associated with butyrate production and anti-inflammatory effect. An n–6/n–3 PUFA proportion of 3/1 to 11/1 in the diet recorded decreased effects of obesity and its related metabolic dysbioses and increased Allobaculum, Isobaculum, Proteobacteria, and Lachnospiraceae. Lachnospiraceae and Allobaculum are associated with SCFA production. Besides, Allobaculum is related to high-lipoprotein density-cholesterol (HLD-C) production and reduction in obesity effect. Unfortunately, the beneficial effect of Isobaculum on health is yet unknown.

28Other studies on n–6 PUFA-rich diets reported increasing effects of obesity, weight gain, inflammation, and adipose tissue fat accumulation. The increase of Bacteroides, Bifidobacterium, Lachnospiraceae Proteobacteria, and Clostridiales is related to metabolic dysfunction risks. Effects of PUFAs on gut microbiota are summarized in Table 6.

29Different types of FA dietary intakes play a crucial role in modifying the composition of gut microbiota, which interplay the health improvement or disease of the host. The consumption of HFD with a predominance of MCFAs, MUFAs, and n–3 (EPA and DHA), including low fat-diet of LCFA dietary intake, increases the beneficial microbiota, mainly the Bacteroidetes to Firmicutes ratio as well as Actinobacteria and Proteobacteria species. These bacterial species are correlated with increasing SCFA production, which prevents and reduces obesity and its related metabolic dysbiosis effects. However, high-fat diets of LCFAs and n–6 PUFA dietary intake present antagonistic effects and show pathologic results to animal models and human studies compared with other types of fatty acids.