Obesity is a highly prevalent disease globally and increases the risk for other chronic conditions like type 2 diabetes mellitus, coronary heart disease, osteoarthritis, sleep apnea, and some types of cancer [1]. Anti-obesity drugs are often used to prevent and treat obesity and its comorbidities; however, various side effects and inflated healthcare costs have resulted in seeking safe and effective natural product alternatives in obesity management [2]. Obesity is a multi-factorial health challenge that is accompanied by immune dysfunction of white adipose tissue and intestinal microbiome dysbiosis; recently, the administration of bacteria or their metabolites from fermented foods has been found to beneficially affect adipose tissue function, inflammation, and the gut microbiome ^{[3][4][5][6][7]}[3,4,5,6,7].

Fermentation has been used for centuries to preserve foods and their texture through deactivating spoilage microorganisms ^[8][9][8,9]. Fermented foods contain enduring microorganisms that predominantly include lactic acid bacteria (LAB) and their major metabolites, i.e., lactate ^[9][10][9,10]. These foods are thought to have health-promoting effects due to a mixture of several beneficial microorganisms—not only LAB species but also acetobacter and Propionibacterium; and bioactive macromolecules—such as exopolysaccharides and bactericides ^{[11][12][13][14]}[11,12,13,14]. However, the mechanisms of action are not entirely clear ^[10][15][10,15].

Regular consumption of fermented foods can exert beneficial effects on body weight regulation and metabolic function through several mechanisms. Although the level of evidence for some types of fermented foods is still very low and there are considerable knowledge gaps regarding the molecular mechanisms of action of specific fermented foods, the current findings are promising. 

2. Fermented Foods, Gut Microbiota, and Metabolic Regulation

Fermented foods function as a relatively optimal drug delivery system as they contain a mixture of safe bioactive compounds in sufficient doses to transfer to the target site, thereby facilitating efficacy and long-term compliance ^[11][16][17][11,16,17]. The food matrix of fermented foods can exert medicinal properties by a large number of viable microorganisms and their transformed metabolites to shield the gastrointestinal tract against pathogens, excess gastric acid, and bile salts ^[18][19][18,19]. Probiotic microorganisms in fermented foods are capable of producing short-chain fatty acids (SCFAs) via fermentation of the prebiotic non-digestible carbohydrates, which can then be taken up as a source of energy by bacteria in the colon, inhibit the overgrowth of intestinal pathogens, and regulate various metabolic pathways (e.g., cholesterol synthesis), including the secretion of appetite hormones ^{[9][20][21][22][23]}[9,20,21,22,23]. Fermented foods also contain live microorganisms or beneficial bioactive compounds that support the symbiosis between the host and the microbiome, resulting in a healthier gut environment ^[10][21][10,21]. SCFAs like acetate, propionate, and butyrate and other primary metabolites of live probiotics from fermented foods can stimulate the growth of beneficial microbial phyla in the gut, for example, by lowering intestinal luminal pH and improving conditions for intestinal commensal microflora like Bacteroides and Prevotella species ^[22][23][22,23]. The association between the gut microbiome and the risk of obesity has been known for some time ^[24][25][26][24,25,26]. Dysbiosis refers to an imbalance of intestinal microflora that is associated with obesity ^[20][27][20,27]. Several experimental and clinical studies have demonstrated that a lower ratio of Bacteroidetes to Firmicutes may be involved in the pathogenesis of obesity; however, due to large inter-individual variation this ratio cannot be considered as a biomarker for increased obesity risk, and further research is required to identify a key bacterial community based on individual characteristics and traits that increases susceptibility to weight gain and body fat accumulation [27]. Although the abundance and composition of healthy gut microflora are different depending on geographical region [28], decreased diversity of the microbial populations is often seen in obese subjects [29]. It remains to be confirmed if manipulation of the microbial community in the gut can result in a long-lasting effect on appetite regulation and body weight homeostasis. Intestinal permeability is another factor that may mediate some of the associations between the gut microbiome and obesity. The microbiome interacts with inflammatory signal transduction pathways via the gram-negative bacteria membrane lipopolysaccharide (LPS), which binds to CD-14 and toll-like receptor-4 (TLR4) on enterocytes, resulting in the translocation of bacteria through the intestinal barrier and an inflammatory response ^[27][30][31][27,30,31]. Relevant studies indicate that gut microbiome dysbiosis can increase intestinal permeability that can then lead to immune cell infiltration from the intestinal epithelium to the white adipose tissue and initiate low-grade systemic inflammation [32]. Increased abundance of the protein zonulin in feces is a marker of abnormally increased gut permeability and disturbed gut barrier function. Recent evidence demonstrates that fermented dairy products, such as kefir, can reduce intestinal permeability and gut tight junction dysfunction ^[33][34][33,34], although this does not necessarily result in beneficial changes in serum pro-inflammatory markers [33]. The bioactive compounds in fermented foods can also exert beneficial effects on adipose tissue function via upregulation of the peroxisome proliferator activator receptor γ 2 (PPARγ2) [24]. Excess fat accumulation in white adipose tissue and reduced lipid turnover lead to increased macrophage infiltration and pro-inflammatory cytokine overproduction that predispose to metabolic dysregulation. PPARγ2 suppresses resistin expression in white adipocytes and improves insulin sensitivity [25]. Activation of PPARγ2 also reduces plasma free fatty acid concentrations (partly because of enhanced insulin-mediated suppression of lipolysis) and improves the plasma lipid profile. Furthermore, it suppresses pro-inflammatory mediators and increases macrophage function in visceral adipose tissue [35]. Understanding the effects of fermented foods on the composition and function of the microbiome can contribute to better nutritional therapies for long-term body weight homeostasis. Since many individuals with obesity can lose weight but cannot maintain it for prolonged periods of time, finding safe and long-term dietary treatments has been of great interest [36]. Fermented foods produce SCFAs in the gastrointestinal tract that can regulate the intestinal microbiome, inhibit inflammatory pathways, and reduce appetite hormones ^[10][20][10,20]. Furthermore, fermented foods may contain live microorganisms or beneficial bioactive compounds that support the symbiosis between the host and the microbiome, resulting in a healthy gut environment ^[10][21][10,21]. SCFAs, including acetate, propionate, and butyrate, are the products of fermentation of dietary non-digestible carbohydrates by gut bacteria. They can inhibit lipid synthesis enzymes, reduce pathogen microorganisms, and supply energy for the intestinal epithelium [37]. SCFAs and other primary metabolites of live probiotics from fermented foods can stimulate the growth of beneficial microbial phyla in the gut; for example, they lower intestinal luminal pH and improve conditions for intestinal commensal microflora like Bacteroides [23] and Prevotella [22] species.