**3. Gut microbiota**

There are trillions of microorganisms in the human body and the coordinated function of these microorganisms is important for the host life. The population of microorganisms in the intestine reaches its highest density. This complex microbial community that forms in the intestinal is the gut microbiota [33]. There are 100 trillion microorganisms in the human intestine. The gut microbiota is mainly formed by five phyla and populations, while the intestine is dominated by bacterial species (phyla Firmicutes and Bacteriodetes). There are also viruses, bacteria, archaea, fungi, phages, nematodes, and protists. There is a symbiotic relationship between microorganisms and their human hosts. Through this symbiotic relationship, microorganisms protect and support the structure of the intestinal mucosa during their evolution. There are at least 150 times more genes in the gut microbiota than in the human genome. And it weighs approximately 1 to 2 kg [34–36]. After birth, the ecosystem of gut microbiota is created by the transfer of maternal bacteria and environmental bacteria and continues to expand until adulthood [36]. Bacteria's quantity in the gastrointestinal tract increases from the proximal part to the distal parts. More than 70% of all body microorganisms are located in the large intestine, which is usually associated with host health and disease. In addition, the lumen has a higher bacterial diversity and the mucosal layer has a lower bacterial diversity [35]. Some environmental parameters that may affect the composition of the gastrointestinal microbiota are water activity, PH, availability of nutrients, oxygen levels, and temperature. The diverse and abundant members of the gut microbiota play an important role in maintaining human health by promoting host cell differentiation, by breaking down food to release nutrients that otherwise would be inaccessible to the host, modulating/stimulating the immune system, and preventing colonization by pathogens they protect the host [33]. The presence of large numbers of bacteria in the gastrointestinal tract causes metabolic activity and biochemical diversity that have interactions with the host physiology [35]. Many factors can shift the balance of gut microbiota, and thus, disrupt gut microbial homeostasis and cause dysbiosis. Dysbiosis usually has detrimental effects and may also have long-term consequences that lead to diseases or disorders, such as diabetes, obesity, and inflammatory bowel disease [33]. Dysbiosis is associated with three different phenomena that can occur simultaneously: losing beneficial organisms, potentially harmful bacteria overgrowth, and losing overall microbial diversity [34]. Bacteriocins, which inhibit the bacterial pathogens growing that cause dysbiosis by their antibacterial action are produced by Lactobacillus Plantarum and Lactobacillus para case [37]. For homeostasis and proper metabolic function gut microbiota's health is crucial. Changes in microbiota composition may lead to diabetes and obesity by affecting homeostasis and substantially altering host metabolism and affecting central appetite mechanisms [36]. Proteobacteria lead to metabolic diseases, such as obesity, because it is associated with dysbiosis [37]. Therefore, potentially new anti-obesity strategies may be proposed by modulating intestinal microbiota with fecal microbiota transplantation or dietary interventions, including probiotics and prebiotics. The suggestion of growing evidence of bariatric surgery's success is because of the procedure's effect on the gut microbiota. Bariatric surgery changes the short-chain fatty acids composition by particular changes in the gut microbiota. Thus, affecting host metabolism, including intestinal hormone secretion and sensitivity of insulin. While *Firmicutes* are abundant in the gut microbiota of obese individuals. *Bacteroidetes* are more abundant in individuals with normal BMI, which break down plant starches and plant fibers for energy, thus specific changes in the gut microbial composition are associated with obesity [36]. The increase in the genus *Lactobacillus*, which belongs to the *Firmicutes phylum* was associated with obesity [37]. For metabolic syndrome and obesity, the gut microbiota is an effective and potential factor. Gut microbiota can also affect insulin resistance and hyperglycemia, which are associated with obesity. The effect of intestinal microbiota on insulin and glucose homeostasis may be due to its effect on changing the relative abundance and composition of bile acid species [36]. Bacteria can produce major neurotransmitters. The microbiota also has the potential to affect other levels of neurotransmitters, including gasotransmitters, steroids, neuropeptides, endocannabinoids, and histamine among others [38]. Gut bacteria are involved in the production of neuroactive metabolites, including γ-aminobutyric acid (GABA) and serotonin, thereby affecting central appetite control. And by the effect on serotonin metabolism, which might also influence glucose homeostasis. The gut microbiota also may affect hepatic lipid metabolism, fat storage, and hepatic triglyceride storage. Some bacterial strains affect satiety and appetite by altering the secretion of gut hormones, including ghrelin, leptin, GLP-1, and PYY, through the hypothalamic neuroendocrine pathways. Gut microbiota by altering mood and modulating reward pathways might also affect feeding behavior. The main factor affecting the activity and composition of the microbiota is diet. The gut microbiota is directly shaped by the various components of the diet [36].
