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

Long-term high-fat dietary intake plays a crucial role in the composition of gut microbiota in animal models and human subjects, which affect directly short-chain fatty acid (SCFA) production and host health. This review aims to highlight the interplay of fatty acid (FA) intake and gut microbiota composition and its interaction with hosts in health promotion and obesity prevention and its related metabolic dysbiosis. The abundance of the Bacteroidetes/Firmicutes ratio, as Actinobacteria and Proteobacteria species are associated with increased SCFA production, reported high-fat diet rich in medium-chain fatty acids (MCFAs), monounsaturated fatty acids (MUFAs), and n–3 polyunsaturated fatty acids (PUFAs) as well as low-fat diets rich in long-chain fatty acids (LCFAs). SCFAs play a key role in health promotion and prevention and, reduction and reversion of metabolic syndromes in the host. Furthermore, in this review, we discussed the type of fatty acids and their amount, including the administration time and their interplay with gut microbiota and its results about health or several metabolic dysbioses undergone by hosts.


Introduction
Fatty acids (FAs) are the principal components of triacylglycerols found in oils and fats, which are the second primary source of dietary energy for humans [1]. 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 [2].
FAs furnish energy (9 kcal per gram corresponding to 20-35% of total calorie intake in adults) [3]; carry fat-soluble vitamins (A, D, E, and K) [4]; constitute the cell-membrane phospholipids; and act on its fluidity and signaling [2], immune system regulation, blood clots, and cholesterol metabolism [5]. The 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 [20][21][22]. Therefore, studies have demonstrated that the energy furnished to the host from diet intake The 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 [20][21][22]. 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 [23][24][25][26]. Also, FA diet has contributed to health promotion and disease prevention, including obesity and its related disorders [27][28][29][30].
Obesity 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 [31][32][33], such as insulin resistance and inflammatory diseases.
The 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.

Medium-Chain Fatty Acids
Medium-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 [34]. 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 [35][36][37][38]. 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 [39][40][41]. 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 [42][43][44][45]. MCFAs have shorter biological half-time and higher stability to lipoperoxidation [34]. 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. Table 1. Effects of medium-chain fatty acid intake on gut microbiota composition and metabolic outcomes in animal models. Abbreviation: ↑ = significant increase; ↓ = significant decrease; ↔ = unchanged; IBD = inflammatory bowel disease; HFD = high-fat diet; MCFAs = medium-chain fatty acids; NASH = nonalcoholic steatohepatitis; and T2DM = type 2 diabetes mellitus.

Host
Several 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 [46]. Furthermore, the increase of the Bacteroidetes to Firmicutes ratio as well as the abundance of Ruminococcaceae, Bifidobacterium, and Lactobacillus are associated with SCFA production [15,50,51]. 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 [51][52][53][54][55]. 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 [50,51,56,57]. The natural sources of MCFAs are human milk (9-15%) and virgin coconut oil (61%), presenting higher composition compared with infant formula (8-42%) [37,38,58,59].
However, 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 [48,49,52,60].
Additionally, another gut microbiota feature is related to the most abundant Firmicutes in the intestine of healthy subjects and followed by relatively increasing Bacteroidetes [82,83]. 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 [84]. 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 [9,85].
Therefore, 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 [86,87]. 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 [83,[88][89][90].
MUFA consumption is associated with reduced effects of obesity and its related metabolic syndromes [91][92][93]. 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 [94,95]. 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 [74,96,97]. Effects of MUFA-rich diet consumption on gut microbiota composition in animal models are summarized in Table 3. Table 3. Effects of monounsaturated fatty acids intake on gut microbiota composition and metabolic outcomes in animal models.

Host
Diets Main Outcomes

Gut Microbiota Metabolic
Mice C57BL/6J (germ free wild-type): healthy male [98] Western diet with 41% energy from fat for 8 weeks  The 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 [15,101,102]. 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 [84,86,87,103].

Polyunsaturated Fatty Acids
The 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 [106]. 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) [107].
In 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 [106,108,109].
Thus, 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 [104,117]. Also, n-3 PUFA intake is related to the abundance of gut microbiota composition and to increasing SCFA production [101,102,118]. Effects of PUFA-rich diet consumption on gut microbiota composition in animal models are summarized in Table 5.   1. LFD n-6/n-3 (3/1) for 6 weeks 2. HFD with n-6/n-3 (9/1) for 6 weeks The 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) [80,96,118,124]. Furthermore, the abundance of the Bacteroidetes to Firmicutes ratio is correlated with increasing SCFA (acetate, propionate, and butyrate acids) production [85,102]. Butyrate is a substrate for colonocytes, and all SCFAs produced are important to biomacromolecular substances linked to homeostasis and disease of the host [9,106].

Conclusions
Different 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.