Additionally, the results of recent studies are consistent with the notion that gut microbiota dysbiosis represents an early indication of inflammation and obesity
. The gastrointestinal system interacts with the dietary components involved, which disrupts the gut microbiota’s balance and alters the secretion profiles of gut peptides
. These disruptions trigger an inflammatory response in the intestinal mucosa, causing damage to the epithelial barrier and enhancing LPS entry into the systemic circulation. LPS and saturated fatty acids can activate TLRs, which are receptors that recognize microbial molecules, on macrophages or intestinal epithelial cells
. This leads to low-grade systemic inflammation. TLRs are also expressed in adipose tissue, where they can be activated by LPS and induce the secretion of inflammatory cytokines, such as TNF-α, IL-6, IL-8, and MCP-1, by macrophages and adipocytes
. These cytokines can attract more inflammatory cells to adipose tissue and worsen the inflammation. Chronic inflammation can also affect the gut microbiota and cause dysbiosis
Gut barrier dysfunction and gut microbiota dysbiosis are linked to a diverse array of pathological conditions, including obesity, T2DM, and inflammatory bowel disease. Intestinal epithelial cells play a key role in maintaining the health of the gut microbiota. These cells form a physical barrier between the gut microbiota and the underlying tissues, preventing the migration of harmful bacteria and small molecules into the systemic circulation. Tight junctions between the epithelial cells function as gatekeepers that regulate the entry of nutrients and other substances into the intestinal epithelium. Dysregulation involving these junctions can lead to gut dysbiosis and intestinal permeability, triggering various pathological conditions.The Firmicutes phylum, including the
Lactobacillus genus, has been linked to obesity and T2DM
[59]. However, some genera in this phylum (e.g.,
Lactobacillus paracasei and
Lactobacillus plantarum) can help to prevent weight gain
[60][61]. Decreased relative abundances of
Bacteroides and
Bifidobacterium, as well as the butyrate-producing
Faecalibacterium prausnitzii and
Roseburia intestinalis, have been associated with obesity
[62][63][64]. In T2DM patients, bariatric surgery increases the relative abundance of
F. prausnitzii while improving glucose homeostasis, low-grade inflammation, and intestinal epithelial permeability
[10][65].
F. prausnitzii is a key producer of butyrate, which serves as an important energy source for intestinal epithelial cells
[66]. Multiple butyrate-mediated mechanisms (e.g., mucin synthesis
[67], reorganization of tight junctions, and upregulation of occludin and Zonula occludens protein 1
[68][69]) can reduce local inflammation and improve intestinal barrier permeability. The species
Bacteroides vulgatus and
Bacteroides dorei may provide benefits for T2DM patients by increasing Zonula occludens protein 1 (ZO-1) expression and enhancing epithelial barrier function
[70]. These bacteria produce bacteriocins, a class of proteins that inhibit the growth of specific microbes and could reduce the abundance of harmful species
[71].
4.3. Muscle
Skeletal muscle, which comprises approximately 40% of the human body mass, is responsible for numerous critical functions including thermoregulation and the modulation of glucose/amino acid metabolism. Although it is physically distinct from the gut, skeletal muscle is influenced by gut-derived signals that arise from interactions between gut microbiota and host tissue; these interactions involve microbes, metabolites, gut peptides, LPS, and ILs. These signals form a link between gut microbiota activity and skeletal muscle function; modulation of these signals influences systemic or tissue inflammation and insulin sensitivity, helping to regulate muscle function. Disruptions in gut microbiota composition can lead to muscle atrophy, weakness, and poor exercise performance. Additionally, some microbial metabolites, such as SCFAs, have direct effects on muscle health and function, highlighting the complex interactions between gut microbiota and muscle physiology. Thus, the gut microbiota represents a promising new target for the prevention and treatment of muscle-related diseases.
Considering the diverse array of gut microbiota-derived metabolites, research has focused on the potential for SCFAs to mediate interactions among the gut microbiota, gastrointestinal physiology, and muscle insulin sensitivity. Comparative analyses have revealed that exercise interventions are associated with greater abundances of SCFA-producing microbial taxa, compared with the abundances in individuals with sarcopenia. SCFAs are primarily generated by microbial anaerobic fermentation of nondigestible dietary fibers, mainly within the distal ileum and colon. Acetate, propionate, and butyrate comprise the predominant SCFA profile within the colon, totaling more than 95% of the total SCFA content. Upon entry into enterocytes, butyrate drives the citric acid cycle through acetyl-CoA, satisfying up to 60–70% of colonocyte metabolic needs
[28]. The remaining SCFAs are transported through the portal vein to the liver, which absorbs up to 80% of the available propionate and 40% of the available acetate for subsequent utilization in gluconeogenesis
[28][72]. Finally, a small subset of SCFAs, predominantly acetate, is transported to skeletal muscle.
SCFAs are important for maintaining glucose and lipid homeostasis, regulating inflammation, and establishing connections between the gut and distant tissues
[28][73]. There is empirical evidence that SCFA supplementation can enhance muscle mass and strength, particularly in germ-free and antibiotic-treated rodents
[74][75][76][77]. Notably, acetate supplementation (via dietary intake or subcutaneous injection) enhances glucose uptake and glycogen content while reducing lipid accumulation in rat skeletal muscles
[78].
5. Conclusions
The cumulative findings of numerous studies highlight the complex and multifaceted link between intestinal microflora and obesity. These studies have demonstrated that gut microbiota dysregulation influences energy equilibrium and can contribute to the onset of obesity. Furthermore, these studies have identified potential mechanisms by which the gut microbiota and its metabolites affect the onset of obesity, including the production of endogenous metabolites, regulation of systemic inflammation, and modulation of the adipose tissue microenvironment.