Microbiome Interactions in Metabolic Diseases

The complex communities of microorganisms that inhabit the gut and other body niches play a crucial role in the regulation of host energy balance, immune tone and metabolic homeostasis. Alterations in microbial composition, termed dysbiosis, can lead to increased intestinal permeability, facilitating translocation of bacterial components such as lipopolysaccharide into the circulation and driving low‐grade inflammation that underpins insulin resistance and adipose tissue dysfunction. Microbial metabolites, notably short‐chain fatty acids and bile acid derivatives, influence glucose and lipid metabolism through receptor‐mediated pathways, while bacterial extracellular vesicles can modulate signalling in skeletal muscle and liver. Animal models and human cohort studies have collectively revealed bidirectional pathways linking diet, microbiome shifts and metabolic end points, highlighting potential targets for prebiotic, probiotic and postbiotic interventions to prevent or treat obesity, type 2 diabetes and related disorders.

Research from Nature Portfolio

A large‐scale survey of nearly ten thousand healthy individuals demonstrated that bacterial DNA detected in blood is sporadic and primarily reflects transient translocation of commensals from the gut, oral cavity and genitourinary tract rather than a stable core blood microbiome. Complementary work has shown that gut microbe‐derived extracellular vesicles, enriched under high‐fat dietary conditions, impair insulin signalling and glucose tolerance when delivered to muscle and adipose tissue, establishing a mechanistic link between microbial vesicles and metabolic inflammation.

Microbiome Interactions in Metabolic Diseases publication trend

The graph below shows the total number of articles in microbiome interactions in metabolic diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Dysbiosis: imbalance in microbial community structure associated with disease states.

Extracellular vesicles: membrane‐bound nanoparticles released by bacteria carrying proteins, nucleic acids and lipids that influence host cell function.

Intestinal permeability: property of the gut barrier that, when increased, allows microbes and metabolites to enter the circulation.

Short‐chain fatty acids: key microbial fermentation products of dietary fibre that regulate host energy metabolism and immune responses.

Metabolic endotoxaemia: chronic low‐grade elevation of circulating bacterial lipopolysaccharide driving inflammation and insulin resistance.

References

1. No evidence for a common blood microbiome based on a population study of 9,770 healthy humans. Nature Microbiology (2023).
2. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle. Scientific Reports (2015).
3. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin. Microbiome (2021).
4. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Molecular Medicine (2011).