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ABSTRACT Perturbations in the intestinal microbiome are implicated in inflammatory bowel disease (IBD). Studies of treatment-naive patients have identified microbial taxa associated with

disease course and treatment efficacy. To gain a mechanistic understanding of how the microbiome affects gastrointestinal health, we need to move from census to function. Bacteria, including

those that adhere to epithelial cells as well as several _Clostridium_ species, can alter differentiation of T helper 17 cells and regulatory T cells. Similarly, microbial products such as

short-chain fatty acids and sphingolipids also influence immune responses. Metagenomics and culturomics have identified strains of _Ruminococcus gnavus_ and adherent invasive _Escherichia

coli_ that are linked to IBD and gut inflammation. Integrated analysis of multiomics data, including metagenomics, metatranscriptomics and metabolomics, with measurements of host response

and culturomics, have great potential in understanding the role of the microbiome in IBD. In this Review, we highlight current knowledge of gut microbial factors linked to IBD pathogenesis

and discuss how multiomics data from large-scale population studies in health and disease have been used to identify specific microbial strains, transcriptional changes and metabolic

alterations associated with IBD. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

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SIMILAR CONTENT BEING VIEWED BY OTHERS EXPLORING HOW MICROBIOME SIGNATURES CHANGE ACROSS INFLAMMATORY BOWEL DISEASE CONDITIONS AND DISEASE LOCATIONS Article Open access 21 September 2021

MICROBIOTA IN INFLAMMATORY BOWEL DISEASE: MECHANISMS OF DISEASE AND THERAPEUTIC OPPORTUNITIES Article 10 March 2025 ASSOCIATION OF DISTINCT MICROBIAL AND METABOLIC SIGNATURES WITH

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authors thank T. Reimels for editorial assistance and for help with figure design. R.J.X. received funding from the US National Institutes of Health (P30 DK043351 and R01 AT009708), the

Crohn’s and Colitis Foundation of America, and the Center for Microbiome Informatics and Therapeutics at MIT. REVIEWER INFORMATION _Nature Reviews Microbiology_ thanks J. Faith, C.

Manichanh, and other anonymous reviewer(s), for their contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Broad Institute of MIT and Harvard,

Cambridge, MA, USA Melanie Schirmer, Ashley Garner, Hera Vlamakis & Ramnik J. Xavier * Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA Hera Vlamakis & 

Ramnik J. Xavier Authors * Melanie Schirmer View author publications You can also search for this author inPubMed Google Scholar * Ashley Garner View author publications You can also search

for this author inPubMed Google Scholar * Hera Vlamakis View author publications You can also search for this author inPubMed Google Scholar * Ramnik J. Xavier View author publications You

can also search for this author inPubMed Google Scholar CONTRIBUTIONS M.S., A.G., H.V., and R.J.X. conceived and wrote the article. All authors substantially contributed to discussion of

content and reviewed/edited the manuscript before submission. M.S. generated Fig. 2. CORRESPONDING AUTHORS Correspondence to Melanie Schirmer, Hera Vlamakis or Ramnik J. Xavier. ETHICS

DECLARATIONS COMPETING INTERESTS R.J.X. is a consultant to Nestle and Novartis. All other authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature

remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. RELATED LINKS INFLAMMATORY BOWEL DISEASE MULTI’OMICS DATABASE. https://ibdmdb.org/

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION GLOSSARY * Microbiota The collection of microorganisms in a particular environment. * Microbiome The genes, genomes and products of the

microbiota. * Barrier function Epithelial cell–cell junctions plus the mucosal layer that permit nutrients and prevent luminal contents from accessing the rest of the body. * Glycaemic

response The glycaemic response to food describes its effect on blood glucose levels after consumption. * Non-caseating granulomas Granulomas are clusters of immune cells that form during

infection, inflammation or in the presence of a foreign substance to prevent a systemic spread. The absence of necrosis is a defining feature of non-caseating granulomas. In Crohn’s disease,

non-caseating granulomas are formed during inflammation without an obvious infectious trigger. * Hygiene hypothesis According to the hygiene hypothesis, a lack of early childhood microbial

exposure affects the development of the immune system. This has been ascribed to the increase of allergic and autoimmune diseases in Western countries. * Mannan A mannose polymer and

component of fungal and plant cell walls. * Atypical perinuclear anti-neutrophil cytoplasmic antibody Anti-neutrophil cytoplasmic antibodies are classified based on staining patterns.

Cytoplasmic anti-neutrophil cytoplasmic antibody (ANCA) refers to staining of the entire cytoplasm, and perinuclear ANCA refers to staining of the area around the nucleus. Perinuclear ANCAs

have been implicated in inflammatory bowel disease; however, their target antigens are unknown and they are therefore described as atypical perinuclear ANCA. * Laminaribioside A glucose

disaccharide building block of laminarin and a component of the cell walls of fungi and algae. * Chitobioside A building block of the _N_-acetylglucosamine-based glycan chitin and a

component of the cell walls of microorganisms. * Mannobioside A disaccharide of mannose. * Colectomy A surgical procedure removing all or part of the colon. * Strains The classical

microbiological definition of strain is a single bacterial isolate. In the context of metagenomic data, it refers to a combination of single-nucleotide polymorphisms that are computationally

predicted to be linked and originating from an individual strain genome. * Metatranscriptome All of the RNA in an environment. * Culturomics The process of using classical microbiological

techniques to culture and identify unknown bacteria that inhabit a given environment. * Indole metabolites Indole metabolites derive from microbial metabolism of tryptophan and can be

recognized by several host receptors that regulate host–microbial homeostasis. * Metagenomes All the genetic material present in an environment, consisting of the genomes of numerous

organisms. * RORγt+ Treg cells Regulatory T cells that express the transcription factor RORγt, a nuclear hormone receptor and critical regulator of antimicrobial immunity. * Autoimmune

polyendocrinopathy–candidiasis–ectodermal dystrophy An autoimmune disease characterized by destruction of endocrine tissues, chronic mucocutaneous candidiasis and ectodermal disorders. * 16S

ribosomal RNA (rRNA) gene A gene conserved among bacteria often used for taxonomic classification. * Keystone taxa Species with high connectivity in microbial networks (built based on

statistical associations), suggesting that they are a key component of the ecosystem and their removal would result in drastic changes to the microbial ecosystem. * Anti-tumour necrosis

factor therapy Drugs that target tumour necrosis factor to decrease inflammation are often used to treat autoimmune diseases and inflammatory bowel disease. * Irritable bowel syndrome A

chronic condition, which affects the large intestine and causes abdominal pain, cramping and shifts in bowel movement patterns. In contrast to inflammatory bowel disease, irritable bowel

syndrome is not associated with mucosal inflammation, ulcers or other damage to the bowel. * Chromogranins and secretogranins A family of water-soluble acidic glycoproteins that are mainly

produced by endocrine cells, such as the enteroendocrine cells of the gut. Also known as granins, they are precursors of biologically active peptides involved in inflammation. * Metabolome

All of the metabolites in an environment. * Probiotic An organism or multiple organisms that confer beneficial effects to the host. * Postbiotic A bacterial metabolic product that mediates

benefits to the host. * Prebiotic A certain food or food component that confers a beneficial effect by providing a competitive advantage to beneficial commensal bacteria capable of

metabolizing these substrates or by augmenting the production of metabolic products that result from their fermentation. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Schirmer, M., Garner, A., Vlamakis, H. _et al._ Microbial genes and pathways in inflammatory bowel disease. _Nat Rev Microbiol_ 17, 497–511 (2019).

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