Overweight, obesity, undernutrition and their respective sequelae have devastating tolls on personal and public health worldwide. Traditional approaches for treating these conditions with diet, exercise, drugs and/or surgery have shown varying degrees of success, creating an urgent need for new solutions with long-term efficacy. Owing to transformative advances in sequencing, bioinformatics and gnotobiotic experimentation, we now understand that the gut microbiome profoundly impacts energy balance through diverse mechanisms affecting both sides of the energy balance equation. Our growing knowledge of microbial contributions to energy metabolism highlights new opportunities for weight management, including the microbiome-aware improvement of existing tools and novel microbiome-targeted therapies. In this Review, we synthesize current knowledge concerning the bidirectional influences between the gut microbiome and existing weight management strategies, including behaviour-based and clinical approaches, and incorporate a subject-level meta-analysis contrasting the effects of weight management strategies on microbiota composition. We consider how emerging understanding of the gut microbiome alters our prospects for weight management and the challenges that must be overcome for microbiome-focused solutions to achieve success.
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This work was supported by grants from the National Science Foundation (BCS-1919892 and BCS-2142073) and William F. Milton Fund to R.N.C. and from the National Institute of Allergy and Infectious Disease (R00AI47165) to J.E.B.
The authors declare no competing interests.
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Diversity of microbial taxa within a given sample; distinct from β-diversity, which indexes differences in microbiome composition between samples.
- Energy balance
The balance between energy intake and expenditure crucial in weight maintenance.
- Faecal microbiota transplantation
(FMT). The experimental or therapeutic administration of preparations of faecal material intended to transfer microbiota-mediated effects to a recipient.
- Germ-free animals
Animals lacking resident microorganisms, which may be derived through sterile surgical birth followed by rearing and propagation under strictly sterile conditions.
- Gnotobiotic mice
Animals born without microorganisms (that is, germ-free) that may be colonized to study effects of microbial colonization on host physiology.
- Gut barrier
Multilayered structure (consisting of mucus with embedded antimicrobial peptides and secretory IgA, epithelial cells and their cell-to-cell junctions, and the immune element-rich lamina propria) that simultaneously allows for nutrient absorption while restricting contact with the gut microbiota and its products.
- Ketogenic diet
A protein-adequate diet marked by high-fat and very-low (<10% kcal) carbohydrate intake that forces the metabolism of stored fat into ketones.
- Low-grade inflammation
Immunometabolic state, marked by the chronic production of low-level inflammatory factors, that bidirectionally potentiates metabolic disease.
- Mediterranean diet
A diet emphasizing plant-based ingredients and unsaturated fats (mainly olive oil), moderate amounts of seafood and poultry and minimal amounts of refined carbohydrates and red meat.
Analysis using the data derived from multiple studies to achieve greater sample size and uncover reproducible findings.
- Metabolic syndrome
A cluster of physiological conditions — including excess visceral fat, high fasting glucose, high triglycerides, low HDL cholesterol and/or high blood pressure — that can together increase the risk of diabetes, heart disease and stroke.
The genetic content and products of a community of microorganisms.
- Microbiome diversity
Measurements of the number of microorganisms/genes present within an individual and/or how evenly they are distributed.
- Microbiome-wide association studies
Studies employing a statistical approach that mines microbiome and host phenotype datasets to identify specific microbial taxa or microbial genes that are associated with specific host traits; also known as metagenome-wide association studies.
A community of microorganisms inclusive of bacteria, fungi, viruses, archaea and protists.
- Roux-en-Y gastric bypass
(RYGB). Bariatric surgery promoting weight loss, in which a small pouch of stomach is connected to the jejunum, thereby restricting food intake and bypassing digestion in the duodenum.
- Short-chain fatty acid
(SCFA). Microbial metabolite resulting from fermentation with wide-ranging effects on host physiology.
A state of deficient energy intake characterized by stunting (low height-for-age), wasting (low weight-for-height) and/or underweight (low weight-for-age) that increases the risk of morbidity and mortality, especially in children.
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Carmody, R.N., Bisanz, J.E. Roles of the gut microbiome in weight management. Nat Rev Microbiol 21, 535–550 (2023). https://doi.org/10.1038/s41579-023-00888-0