Gut Microbiota Modulation in Metabolic and Inflammatory Disorders

The gut microbiota forms a complex ecosystem that interfaces with host metabolism and immunity, influencing the onset and progression of metabolic disorders such as obesity, non-alcoholic fatty liver disease and type 2 diabetes, as well as inflammatory conditions including inflammatory bowel disease and colitis. Modulation of this microbial community through dietary fibres, prebiotics, probiotics and postbiotics can restore ecological balance, reinforce intestinal barrier function, regulate bile acid profiles and modulate host signalling pathways. Disruptions in microbial diversity or function—often termed dysbiosis—can compromise barrier integrity, elevate systemic lipopolysaccharide levels and trigger low-grade inflammation, which perpetuates insulin resistance and hepatic steatosis. Advances in metagenomic, metabolomic and gnotobiotic models have revealed specific bacterial species and their metabolites that hold therapeutic promise for alleviating metabolic inflammation. Strategies that leverage microbial enzymes to generate beneficial short-chain fatty acids or odd-chain fatty acids, or that target host receptors such as the aryl hydrocarbon receptor, are emerging as precision approaches to mitigate metabolic and inflammatory disorders on a global scale.

Research from Nature Portfolio

One investigation in mouse models of non-alcoholic steatohepatitis demonstrated that a commensal bacterium can ferment inulin into pentadecanoic acid, an odd-chain fatty acid, which restores gut barrier integrity and reduces liver inflammation. A separate study employed broad-spectrum antibiotics to deplete gut microbes, revealing that such depletion shifts colonocyte energy metabolism from short-chain fatty acids to glucose, lowers baseline serum glucose and enhances insulin sensitivity by altering luminal signalling and bile acid pools. Another approach explored a poly-saccharide-rich extract from a medicinal fungus, which reversed high-fat diet-induced dysbiosis, reduced circulating endotoxin levels and attenuated systemic inflammation, highlighting the potential of high-molecular-weight prebiotic compounds to modulate microbiota composition and ameliorate obesity-associated metabolic dysfunction.

Gut Microbiota Modulation in Metabolic and Inflammatory Disorders publication trend

The graph below shows the total number of articles in gut microbiota modulation in metabolic and inflammatory disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Gut microbiota: The community of microorganisms residing in the gastrointestinal tract.

Dysbiosis: An imbalance in microbial composition or function associated with disease.

Postbiotics: Non-viable bacterial products or metabolites that confer health benefits.

Short-chain fatty acids (SCFAs): Microbial fermentation products, such as acetate, butyrate and propionate.

Aryl hydrocarbon receptor (AhR): A host transcription factor activated by microbial and dietary ligands.

Intestinal barrier integrity: The selective permeability of the gut epithelium that prevents systemic translocation of microbes and toxins.

References

1. Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid. Nature Microbiology (2023).
2. Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nature Communications (2018).
3. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nature Communications (2015).
4. Postbiotic Impact on Host Metabolism and Immunity Provides Therapeutic Potential in Metabolic Disease. Endocrine Reviews (2024).
5. The gut microbiota‐aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol‐rich extracts from Sanghuangporus. iMeta (2024).
6. Gut microbiome and health: mechanistic insights. Gut (2022).