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  • Review Article
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Microbiome risk profiles as biomarkers for inflammatory and metabolic disorders

Nature Reviews Gastroenterology & Hepatology volume 19, pages 383–397 (2022)Cite this article

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Abstract

The intestine harbours a complex array of microorganisms collectively known as the gut microbiota. The past two decades have witnessed increasing interest in studying the gut microbiota in health and disease, largely driven by rapid innovation in high-throughput multi-omics technologies. As a result, microbial dysbiosis has been linked to many human pathologies, including type 2 diabetes mellitus and inflammatory bowel disease. Integrated analyses of multi-omics data, including metagenomics and metabolomics along with measurements of host response and cataloguing of bacterial isolates, have identified many bacteria and bacterial products that are correlated with disease. Nevertheless, insight into the mechanisms through which microbes affect intestinal health requires going beyond correlation to causation. Current understanding of the contribution of the gut microbiota to disease causality remains limited, largely owing to the heterogeneity of microbial community structures, interindividual differences in disease evolution and incomplete understanding of the mechanisms that integrate microbiota-derived signals into host signalling pathways. In this Review, we provide a broad insight into the microbiome signatures linked to inflammatory and metabolic disorders, discuss outstanding challenges in this field and propose applications of multi-omics technologies that could lead to an improved mechanistic understanding of microorganism–host interactions.

Key points

  • Several commonalities exist between inflammatory bowel disease (IBD) and type 2 diabetes mellitus (T2DM), two multifactorial diseases that show a pattern of increasing global incidence following industrialization.

  • Altered gut bacterial composition and changes in host processing of bacteria-derived metabolites are implicated in IBD and T2DM and provide a shared underlying pathogenetic mechanism.

  • A causal link between dysbiotic microbial communities and IBD or T2DM has been established through gnotobiotic mouse experiments and integrative multi-omics studies.

  • Challenges in disease-specific biomarker discovery include determining the causality of observed changes, understanding their functional redundancy in disease mechanisms and the geographic and ethnic heterogeneity of gut microbiota.

  • Big data refinement, testing and validation of specific bacterial strains, their encoded genes and metabolic byproducts are necessary to identify disease biomarkers.

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Fig. 1: Bacterial risk signatures in the gut microbiomes of patients with IBD or T2DM.
Fig. 2: Overlapping global risk profiles in IBD and T2DM.
Fig. 3: Gut microbiome signature discovery in IBD and T2DM.

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Acknowledgements

The authors’ research is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – project number 395357507 (SFB 1371, Microbiome Signatures) — and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 964590.

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Authors and Affiliations

  1. Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany

    Amira Metwaly & Dirk Haller

  2. ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany

    Sandra Reitmeier & Dirk Haller

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  1. Amira Metwaly
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Contributions

A.M. and D.H. contributed equally to all aspects of the article. In addition, S.R. researched data for the article, contributed substantially to discussion of its content, and reviewed and/or edited the manuscript before submission.

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Correspondence to Dirk Haller.

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Nature Reviews Gastroenterology & Hepatology thanks Herbert Tilg, Chaysavanh Manichanh and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Microbiome

All the microorganisms, their genomes and the surrounding host-shaped environmental conditions of a given habitat. The gut microbiome can be characterized through the application of metagenomics, metabolomics, metatranscriptomics and metaproteomics combined with clinical or environmental metadata.

Microbiota

The microorganisms (bacteria, fungi, archaea and viruses) of a defined environment.

Microbiome signatures

Unique patterns of microbiome configuration that can stratify defined physiological and pathological conditions and can be used to predict the risk of disease development or progression.

Pathobionts

Microorganisms that are linked to chronic inflammatory conditions but are harmless to the host under normal conditions.

Faecal microbiota transplantation

(FMT). A treatment based on transfer of microorganisms from the stool of a healthy donor into a patient’s digestive system.

Dysbiosis

(Also known as pathobiome). An altered microbial community composition that affects the host immune response and leads to the emergence and outbreak of pathogens.

Specificity

The proportion of individuals who genuinely do not have the disease or condition and receive negative test results.

Sensitivity

The proportion of individuals who genuinely have the disease or condition and receive positive test results.

Diagnostic biomarkers

Characteristics that are directly linked to the aetiology of the disease such as elevated blood glucose concentration (which is diagnostic of type 2 diabetes mellitus) and markers that show a strong correlation with inflammation in inflammatory bowel disease (such as faecal calprotectin levels).

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Metwaly, A., Reitmeier, S. & Haller, D. Microbiome risk profiles as biomarkers for inflammatory and metabolic disorders. Nat Rev Gastroenterol Hepatol 19, 383–397 (2022). https://doi.org/10.1038/s41575-022-00581-2

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