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Gut microbiota in human metabolic health and disease

Nature Reviews Microbiology volume 19, pages 55–71 (2021)Cite this article

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Abstract

Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field.

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Fig. 1: Impact of diet on gut microbiota and host metabolism.
Fig. 2: Some of the reported intestinal microbial taxonomic and functional features linked to common metabolic disorders.
Fig. 3: Microbial messengers regulate host metabolism.

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Acknowledgements

This study was supported by Marie Skłodowska-Curie Individual Fellowship 797267 (granted to Y.F.). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research centre at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation.

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  1. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Yong Fan & Oluf Pedersen

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  1. Yong Fan
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Glossary

Supervised machine learning

A form of applied artificial intelligence where the algorithm learns by experience to classify new data according to prior labels.

Random forest

A machine learning approach where a multitude of algorithms (decision trees) are used to optimize, for instance, classification or regression of data sets.

Kyoto Encyclopedia of Genes and Genomes

A publicly available database in bioinformatics and system medicine-driven analyses with information on omics-generated data, biological pathways, chemicals and drugs.

Dysmetabolism

Metabolic dysfunctions often including abdominal obesity, dyslipidaemia and higher blood glucose and higher blood pressure than normal.

Endotoxaemia

The presence of endotoxin(s) within the blood, for example, bacterial lipopolysaccharides.

Dyslipidaemia

An abnormal amount and an abnormal relative distribution of various lipids in the blood.

Atherogenesis

The dynamic process of forming atheromas (also called plaques), that is, accumulated inflammatory cells, lipids, cell debris, minerals and connective tissue in and on the walls of an artery forming a swelling that narrows the arterial lumen and restricts the flow of blood.

Thrombosis

The formation of a blood clot, known as a thrombus, within a blood vessel. The blood clot that consists of platelets, red blood cells and fibrin proteins obstructs the flow of blood through the blood vessel.

Stroke

An acute brain insult where compromised blood flow in atherosclerotic arteries or bleeding from brain arteries causes damage to brain tissues often resulting in various paresis.

Myocardial infarction

(Also known as an acute heart attack or acute coronary syndrome). An event that occurs when blood flow is acutely compromised or is completely stopped to a part of the heart muscle (myocardium), causing severe damage to the heart.

Atherosclerosis

The build-up of cholesterol, other lipids, inflammatory cells and calcium in artery walls, which can restrict blood flow.

Atherothrombosis

The formation of a blood clot within an artery that is affected by arteriosclerosis.

Plaque instability

Vulnerable arterial wall plague that intermittently ruptures giving rise to circulating plaque fragments called emboli, which may cause myocardial infarction or stroke.

Intima

The innermost coating of the vessel wall including the endothelial surface at the lumen.

Steatosis

An abnormal retention of lipids within an organ. The term is most often used about a fatty liver.

Portal endotoxaemia

Endotoxins, primarily bacterial lipopolysaccharides, which are absorbed from the intestines into mensenteric and liver veins (portal drainage).

Liver cirrhosis

A chronic liver disease caused, for instance, by alcohol abuse or virus infection with impairment of multiple liver functions owing to replacement of normal liver tissues by scar tissue.

Hepatic encephalopathy

A spectrum of cognitive and neuro-psychiatric abnormalities such as personality changes, anxiety, confusion, fatigue, shaky hands or seizures caused by severely impaired liver function.

Holobiont

The unique and discrete collective of a macro-organism — a host — and the complex microbial communities for which the macro-organism is the habitat.

Anorexigenic hormones

These appetite-decreasing hormones include glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), both produced by specialized intestinal cells and leptin produced by adipocytes and intestinal cells.

Leptin

A hormone predominantly synthesized in adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes.

Hyperinsulinemia

A state where the concentration of insulin in blood is higher than what is considered normal.

Hyperphagia

An abnormally great desire for food.

Ghrelin

A circulating hormone that is produced mainly by stomach cells and that stimulates appetite and promotes fat storage.

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Fan, Y., Pedersen, O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 19, 55–71 (2021). https://doi.org/10.1038/s41579-020-0433-9

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