The most recent studies comparing the gut microbiome in adults with obesity and control groups have demonstrated that gut microbiota diversity in obese people is significantly decreased, and there are significant differences between the microbiota of these two groups at different levels, from phylum to species. Furthermore, it has been shown that obese people have abnormalities mainly with respect to carbohydrate and lipid metabolism pathways compared to the control group ^[1][2][3][4][68,69,70,71]. Additionally, comparing the structure of the gut microbiota between obese and normal school-age children revealed that the gut microbiota in obese children was less diverse than in the control group. In addition, a significant difference in the relative frequency of gut microbiota was observed at different classification levels ^[5][72]. On the other hand, there is evidence indicating that the composition of the gut microbiome can enhance dietary energy intake and subsequently contribute to the obese phenotype ^[6][73]. A dietary fiber that cannot be entirely hydrolyzed by human enzymes during digestion is catabolized by gut microbiota, with SCFAs being the main product of this process ^[7][74]. SCFAs can affect the proper function of tight junctions between epithelial cells and subsequently regulate the absorption of xenobiotics. It has also been proved that these molecules can affect appetite, immune system, and blood pressure regulation, as well as lipid and glucose metabolism ^[6][8][73,75].

Some studies have reported that the dominant bacteria living in the intestine belong to four bacterial phylotypes: Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Bacteroidetes and the Firmicutes make up more than 90% of the gut microbiota ^[9][76]. Although some reports have suggested that the gut microbiota in healthy people has a high ratio of Bacteroidetes to Firmicutes, and this ratio is reversed in obese individuals, with a lower frequency of Bacteroidetes ^{[3][10][11][12]}[70,77,78,79], other reports have not found this relationship ^[2][13][69,80]. Some studies have even observed an inverse relationship ^[1][14][68,81].

2. Influence of Anti-Inflammatory Diet on Gut Microbiota, Insulin Signaling, and Obesity

Typically, anti-inflammatory diets include the consumption of unrefined and minimally processed foods, nutrients including fiber, mono- and poly unsaturated fatty acids, lean protein sources such as chicken, and various spices, and reducing the consumption of red meat, high-fat dairy foods, and saturated and trans fats that have notably been shown to diminish inflammation ^[15][16][89,90]. The effect of an anti-inflammatory diet on weight loss has been reported many times. For instance, a randomized controlled trial (RCT) study examining the metabolic level and inflammatory status of 81 participants indicated that an anti-inflammatory diet led to a significant decrease in body weight and visceral adipose tissue and improved the cardiometabolic and inflammatory status of the participants ^[17][91]. Moreover, a cross-sectional study on 535 adolescent boys found that adherence to a diet with a low inflammatory index score was related to a reduction in body fat percentage ^[18][92]. Various studies have demonstrated that gut microbiome diversity is influenced by diet ^[19][20][93,94], and that the microbiome is directly involved in regulating pro-inflammatory and anti-inflammatory responses in the gut ^[21][15]. A systematic 2022 review of RCTs in adults, including 18 trials on 1385 obese individuals who were subjected to several dietary interventions, including standard and healthy diets, revealed that diets modified the microbiota signature in a macronutrient composition-dependent manner, so that the percentage of carbohydrates, fats, and fibers seemed to be the primary regulator of the composition, richness, and function of the microbiome, while the increase in protein had relatively few effects on the species and genera. Standard diets, including low-carbohydrate, low-fat, or Mediterranean diets, lead to lower weight and BMI, while other healthy diets promoting whole grains, fruits, and vegetables may or may not be associated with weight loss ^[22][95]. In the following sections, the effect of anti-inflammatory diets on the gut microbiome and obesity will be discussed. Due to the difficulty of conducting controlled dietary intervention trials in humans, most relevant studies have been conducted on animals. However, in the following sections, the authors have attempted to summarize and discuss the human studies.

2.1. Mediterranean Diet

The Mediterranean diet includes consumption of plant foods (high amounts), olive oil (the primary source of fat), dairy products (mainly cheese and yogurt), low to moderate amounts of fish and chicken, zero to four eggs per week, low amounts of red meat, and minor to moderate amounts of wine, typically consumed with meals ^[23][96]. Recently, a systematic review of RCTs reported that the Mediterranean diet could produce significant differences in interleukins-1α, -1β, -4, -5, -6, -7, -8, -10, and -18, IFN-γ, TNF-α, CRP, and hs-CRP compared to the control diet ^[24][97]. Findings on the association between following a Mediterranean diet and the risk of overweight/obesity have been conflicting; therefore, a meta-analytical study was conducted in 2022 showing that following a Mediterranean diet is inversely associated with the risk of overweight and/or obesity ^[25][98]. There is a lot of evidence supporting the beneficial effects of the Mediterranean diet on gut microbiota in preventing obesity. Several reports have elucidated that the consumption of whole grains, which have been reported to reduce inflammation and body weight, is accompanied by a change in the intestinal microbiota in terms of species and gender ^{[26][27][28][29][30]}[99,100,101,102,103]. Examination of the microbiome of 1425 individuals in four cohort studies, including individuals with Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and healthy subjects, revealed that consumption of processed foods and animal-derived foods were related to higher frequencies of Firmicutes and Ruminococcus species and endotoxin synthesis pathways. On the other hand, it was clarified that plant foods and fish were positively associated with SCFA-producing bacteria and nutrient metabolism pathways ^[21][15]. Less adherence to the Mediterranean diet was associated with higher Firmicutes–Bacteroidetes ratio, while better adherence to the Mediterranean diet was associated with a greater abundance of Christensenellaceae and higher SCFA levels ^[31][104]. A systematic review study in 2020 on the impact of dairy products and derivatives on the intestinal microbiota demonstrated that the consumption of dairy products (milk, yogurt, and kefir) enhanced the abundance of beneficial genera Lactobacillus and Bifidobacterium, while consumption of dairy derivatives (whey and casein) and the amount of dairy consumed did not change the composition of the gut microbiota ^[32][105]. An investigation on 360 Spanish adults revealed that high adherence to the Mediterranean diet increased the abundance of certain health-related bacterial species, with the species Bifidobacterium animalis showing the strongest association. In addition, this researchtudy found that some SCFA-producing bacteria were also associated with the Mediterranean diet ^[33][106]. However, a 2022 systematic review of RCTs and observational studies on the effects of the Mediterranean diet on gut microbiota and microbial metabolites indicated that, overall, there is no clear evidence of a consistent effect of the Mediterranean diet on gut microbiota composition or metabolism ^[34][107].

2.2. Dietary Fiber

In general, dietary fiber comprises soluble and insoluble carbohydrates from plant sources that are not digested by human enzymes, are not absorbed in the small intestine, and have positive effects on human health ^[35][108]. There has been extensive research on the relationship between dietary fiber and obesity, the results of which show a significant effect of fiber consumption in reducing obesity ^[35][36][37][108,109,110]. On the other hand, it has been demonstrated that the intake of dietary fiber changes the composition and activity of gut microbiota ^[38][39][111,112]. Both epidemiological and randomized controlled studies have confirmed that receiving a greater abundance of nutritional fiber is associated with a reduction in the risk of Type 2 diabetes ^[40][113]. Some evidence has revealed that the impact of dietary fiber consumption on improving insulin sensitivity is due to an increase in the colonic production of the SCFAs acetate, propionate, and butyrate, the final products of the fermentation of dietary fiber by the gut microbiota ^[41][42][114,115]. Indeed, the anti-inflammatory effects of high circulating concentrations of SCFAs achieved by consuming high-fiber diets have been demonstrated in mouse models. A similar human study discovered that both acetate and propionate were significantly increased in people who consumed a high-fiber diet compared to the low-fiber group, but no changes in peripheral blood inflammatory factors were observed in the five-day intervention; this might be due to the short intervention time ^[43][116]. A comparison of gut microbiota and SCFAs in American women and Ghanaian women (who consumed notably more dietary fiber) indicated that lean Ghanaians had a greater abundance of microbial genes that catalyze the production of butyric acid through the fermentation of pyruvate or branched-chain amino acids. Meanwhile, in obese Ghanaians and American women (regardless of BMI), a higher frequency of microbial genes related to enzymes related to the fermentation of amino acids such as alanine, aspartate, lysine, and glutamate was observed ^[44][117].

2.3. Polyphenols

Polyphenols are secondary plant metabolites that are probably the most abundant antioxidants in daily food intake. Due to their high molecular weight and complex structure, a small percentage of dietary polyphenols is absorbed within the digestive tract. Still, in the large intestine, they are converted into bioactive phenolic metabolites with low molecular weight by the intestinal microbiota ^[45][118]. Various clinical trials have been performed on the impact of polyphenols on intestinal microbiota and obesity, revealing the positive effect of these components in terms of changing the gut microbiota to reduce obesity ^[46][119]. More recent findings also confirm the previous results. For instance, in a double-blind RCT on 62 girls with obesity aged 6–10 years old for 12 weeks, decaffeinated green tea polyphenols were shown to have a significant effect on alleviating obesity and delaying early sexual development ^[47][120]. A randomized, double-blind, parallel clinical trial on 72 obese and overweight volunteers over 16 weeks suggested that polyphenol supplementation significantly reduced body fat mass ^[48][121]. The results of a controlled clinical trial demonstrated that daily consumption of oranges has a positive effect on the composition and activity of intestinal microbiota, such that it has increased the population of Bifidobacterium and Lactobacillus species, and increased SCFA production. In addition, it improved metabolic biomarkers such as low-density lipoprotein (LDL)-cholesterol, glucose, and insulin sensitivity ^[49][122]. An RCT study reported that consumption of genistein (from the flavonoid family) for two months in obese people caused a decrease in insulin resistance, a reduction in metabolic endotoxemia, an increase in the phosphorylation of 5′-adenosine monophosphate-activated protein kinase, and an increase in the oxidation of skeletal muscle fatty acids (via expressing genes involved in fatty acid oxidation) by causing changes in the intestinal microbiota, especially by means of an increase in the Verrucomicrobia phylum ^[50][123]. Polyphenols are an essential component of fiber-containing foods and should be considered when studying the role of fiber-containing foods in human health ^[51][124]. A diet rich in fiber that was enriched with polyphenols and vegetable protein, significantly changed the fecal microbiota in patients with type 2 diabetes compared to the control group. It increased the number of Faecalibacterium prausnitzii and Akkermansia muciniphila, two types of bacteria known to have anti-inflammatory effects, while it decreased the number of Prevotella copri. Along with these changes, a significant decrease in the biomarkers of glucose, triglycerides, total and LDL-cholesterol, HbA1c, CRP, and FFAs, and an increase in antioxidant activity were reported for the intervention group ^[52][125]. In a dietary intervention on mildly hypercholesterolaemic subjects, it was shown that olive pomace (rich in polyphenols and fibers) helped. However, while it did not affect the diversity of the fecal microbiota, it caused a decreasing trend of lactobacilli and Ruminococcus and an increasing trend of Bifidobacteria in the microbiota of the participants. In addition, a considerable increase in the metabolic output of the intestinal microbiota of these subjects was observed, which is probably due to these changes ^[53][126]. The results of an RCT in subjects with high cardiometabolic risk confirmed that diets rich in polyphenols increased the diversity of the dominant fecal bacteria in these individuals, and these changes were connected to changes in glucose/lipid metabolism ^[54][127].

2.4. Omega-3-Rich Diet

Long-chain polyunsaturated fatty acids (LC) are fatty acids with 18 or more carbons, and are classified into two leading families, ω3 (LCn3) and ω6 (LCn6), depending on the position of the first double bond from the methyl end group of the fatty acid ^[55][128]. A 2017 meta-analysis of RCTs found that omega-3 supplementation did not effectively reduce body weight, but reduced waist circumference and triglyceride levels in overweight and obese adults. However, due to the small number and poor quality of the RCTs available in the meta-analysis, it was suggested that more studies be conducted in this field ^[56][129]. Another meta-analysis study of RCTs investigating the effects of supplementation with omega-3 fatty acids on metabolic status in pregnant women reported an increase in serum high-density lipoprotein (HDL)-cholesterol concentration and a decrease in CRP in the participants ^[57][130]. A case study of a healthy 45-year-old man found that an omega-3-rich diet reduced species diversity in the subject’s microbiota but increased the diversity of several butyrate-producing bacteria. In fact, this effect on the microbiota was observed at the genus/species level instead of at the phylum level ^[58][131]. Another study on 22 healthy participants found that high doses of omega-3 supplements did not cause significant changes in the gut microbiome at the phylum level in the volunteers. However, they caused a reversible increase in the abundance of several SCFA-producing genera ^[59][132]. Some findings from an investigation of 47 healthy adults showed that ω-3 fatty acid supplementation had little effect on the gut microbiota. However, increased colonic bacterial diversity after ω-3 fatty acid supplementation was significantly predictive of decreased colonic prostaglandin E2 concentrations ^[60][133]. The results of an RCT in subjects with high cardiometabolic risk reported that diets rich in LCn3 affected the composition of the gut microbiota in these people. It has been shown that the diversity of dominant fecal bacteria decreased after low-LCn3 and polyphenols and High-LCn3 diets, and these changes were connected to changes in glucose/lipid metabolism ^[54][127]. Another study on 126 participants with borderline hypercholesterolemia indicated that during the dietary intervention, the relative abundance of a single species, Clostridium leptum, increased dramatically, and along with that, various plasma markers of the metabolic health status improved, including apolipoprotein B, triglyceride, and the ratio of total cholesterol to HDL. In this researchtudy, butyrate production was discussed as a possible process for improving blood lipid profile ^[61][134].

2.5. Probiotics

Probiotics are non-pathogenic microorganisms that reach the gut in an active state and have potential benefits for the host ^[62][135]. Various reports have described the beneficial effects of probiotics on factors related to inflammation and obesity, as well as their impact on the intestinal microbiota ^[63][64][136,137]. Bifidobacterium and lactobacillus (probiotic yogurt) caused significant decreases in the serum levels of IL-1β, TNF-α, and CRP, as well as considerable increases in the serum levels of IL-6 and IL-10 in the intervention group ^[65][138]. A double-blind RCT in obese women demonstrated that a low-energy diet per se induces changes in metabolite profiles related to reduced inflammation and positive effects on body weight. In addition, it showed that both probiotics and synbiotics produce changes in metabolites associated with improved metabolic health. Finally, it suggested that synbiotics (due to specific metabolite changes) along with a low-energy diet could be more beneficial than probiotics or diet alone ^[66][139]. A synbiotic is a mixture of living microorganisms and substrate(s) selectively used by host microorganisms that is beneficial to host health ^[67][140]. The results of a 2021 meta-analysis of RCTs indicated that probiotic consumption significantly reduced total cholesterol, triglycerides, and LDL-cholesterol levels ^[68][141]. An RCT reported in 2022 revealed that supplementation of the studied probiotics significantly improved the function of the intestinal barrier, leading to a significant reduction in concentrations of lipopolysaccharides (LPS). It also substantially increased HDL-cholesterol and SCFA levels (propionic and butyric acid) and improved obesity-related biomarkers ^[69][142]. Treatment with multispecies probiotics changed the biochemical, physiological, and immunological parameters of the gut microbiota in postmenopausal women with obesity but did not affect diversity or taxonomic classification ^[70][143]. In contrast, the use of probiotics and the Mediterranean diet in overweight breast cancer survivors resulted in a significant increase in the number and diversity of bacterial species in the group that consumed probiotics. In addition, the ratio of Bacteroidetes/Firmicutes decreased in the intervention group, while it increased in the control group. Apart from this, the parameters body weight, BMI, fasting glucose, and insulin resistance exhibited significant decreases in both groups, but in the intervention group, waist circumference, waist/hip ratio, and fasting insulin has also revealed a considerable decline ^[71][144].