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Obesity has become a major public health crisis, with hundreds of millions of people classified as overweight in recent decades.[1][2][3] A vast number of research studies are investigating methods to mitigate this threat to human health. Obesity is the excessive fat accumulation in body tissues, most commonly measured by body mass index (BMI). However, the causes of obesity are numerous and very complex. Many biomedical, socioeconomic, cultural, and other factors contribute to the onset of obesity. Characteristic Western lifestyle features, including energy-intense diets, high meat consumption, a sedentary lifestyle, and the consumption of ultra-processed foods contribute to this phenomenon.[4][5][6][4] The impact of other factors is less well understood, such as a family history of obesity and stress.[7] Therefore, practitioners must treat patients with obesity holistically and comprehensively. One contributor to the pathophysiology of obesity that has garnered particular interest is the composition of gut microbiota, which may be defined as the microbes that live on us and within us.[8] The microbiota genome may be referred to as the "microbiome." Research into the role of gut microbiota affecting host metabolism and homeostasis and their effect on disease processes began with Metchnikoff in the early 1900s. Trillions of microbes occupy the gastrointestinal tract, mainly in the colon. These microbes exist in a complex ecosystem that interacts in tandem with human metabolic activity and a highly diverse microbiome.[2][9] Recent literature has shown how diet influences the composition of gut microbiota and how diet can cause obesity. Nevertheless, much controversy exists regarding the precise mechanisms by which gut microbiota contribute to obesity. This activity for healthcare professionals is designed to enhance the learner's competence in recognizing the significance of the interactions between gut microbiota and enteroendocrine hormone regulation and their relation to excessive adipose accumulation, in particular, the pathophysiologic mechanisms of the permeation of the intestinal barrier, the influence of the gut-brain axis on eating behavior, and nonalcoholic fatty liver disease.

Interaction Between Gut Microbiota and the Gut-Brain Axis The SCFAs produced by gut microbiota also interact with gut hormone signaling to affect eating behavior. These SCFAs interact with the host metabolism by binding to specific G-protein coupled receptors (GPR), including GPR41 and GPR43, causing the release of the peptide tyrosine-tyrosine (PYY), which enters circulation and interacts with the hypothalamus to reduce overall food intake.[38] A specific SCFA, butyrate, is believed to reduce energy expenditure by increasing plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide, and PYY.[1] In a randomized clinical trial, propionate, another SCFA, also was found to cause the release of PYY and GLP-1. Still, propionate also upregulates genes involved in intestinal gluconeogenesis by binding to GPR41, thereby reducing adiposity.[39] Literature also shows that gut microbiota may be directly involved in stimulating the vagal nerve, at least partially through the release of GLP-1, PYY, and cholecystokinin by enteroendocrine cells, which transmits information from the gut to the hypothalamus to regulate appetite and energy homeostasis.[32][33][40][41] Gut microbiota also influences the release of serotonin and gamma-aminobutyric acid, which control host appetite and energy regulation.[42] Gut Microbiota and Fatty Liver Disease Gut microbiota dysbiosis has also been linked with hepatic steatosis associated with obesity.[43] Patients with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly nonalcoholic fatty liver disease or NAFLD) usually experience gut bacteria overgrowth and decreased intestinal barrier integrity. Research shows that worsening of MASLD is associated with increased Bacteroides populations, and hepatic fibrosis correlates with increased Ruminococcus.[44] Gut microbiota is also indirectly involved with triglyceride deposition in the liver via interactions with fasting-induced adiposity factor. Fasting-induced adiposity factor is a lipoprotein lipase inhibitor released by enterocytes whose expression is inhibited by gut microbiota.[45] Fasting-induced adiposity factor also activates carbohydrate-responsive element-binding protein and sterol regulatory element-binding protein 1, which ultimately upregulates triglyceride production and accumulation in the liver.