Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation Journal Article
| Authors: | Becattini, S.; Sorbara, M. T.; Kim, S. G.; Littmann, E. L.; Dong, Q.; Walsh, G.; Wright, R.; Amoretti, L.; Fontana, E.; Hohl, T. M.; Pamer, E. G. |
| Article Title: | Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation |
| Abstract: | The gut microbiota produces metabolites that regulate host immunity, thereby impacting disease resistance and susceptibility. The extent to which commensal bacteria reciprocally respond to immune activation, however, remains largely unexplored. Herein, we colonized mice with four anaerobic symbionts and show that acute immune responses result in dramatic transcriptional reprogramming of these commensals with minimal changes in their relative abundance. Transcriptomic changes include induction of stress-response mediators and downregulation of carbohydrate-degrading factors such as polysaccharide utilization loci (PULs). Flagellin and anti-CD3 antibody, two distinct immune stimuli, induced similar transcriptional profiles, suggesting that commensal bacteria detect common effectors or activate shared pathways when facing different host responses. Immune activation altered the intestinal metabolome within 6 hours, decreasing luminal short-chain fatty acid and increasing aromatic metabolite concentrations. Thus, intestinal bacteria, prior to detectable shifts in community composition, respond to acute host immune activation by rapidly changing gene transcription and immunomodulatory metabolite production. © 2021 Elsevier Inc. Becattini et al. show that activation of the host immune system rapidly alters gene transcription in symbiotic bacteria inhabiting the intestinal lumen, with minimal changes in microbiota composition. Transcriptional changes in resident bacteria alter production of SCFAs and other microbe-derived metabolites, with potential consequences for host immunity and health. © 2021 Elsevier Inc. |
| Keywords: | controlled study; gene sequence; nonhuman; mouse; animal tissue; animal experiment; animal model; genetic transcription; transcriptomics; immune response; stress; innate immunity; immunomodulation; immunostimulation; gene dosage; bacterial colonization; ribosome rna; adaptive immunity; intestine flora; rna 16s; transcriptome; bacterial gene; operon; flagellin; bacterial polysaccharide; microbiota; bacteroidetes; firmicutes; amino acid metabolism; cd3 antibody; immune status; physiological stress; immune responses; male; priority journal; article; rna sequencing; short chain fatty acid; carbohydrate metabolism; metabolome; accute inflammation; meta-transcriptome; polysaccharide utilization loci; pul; scfa |
| Journal Title: | Cell Host & Microbe |
| Volume: | 29 |
| Issue: | 3 |
| ISSN: | 1931-3128 |
| Publisher: | Cell Press |
| Date Published: | 2021-03-10 |
| Start Page: | 378 |
| End Page: | 393.e5 |
| Language: | English |
| DOI: | 10.1016/j.chom.2021.01.003 |
| PUBMED: | 33539766 |
| PROVIDER: | scopus |
| PMCID: | PMC7954923 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work