---
title: "Distribution of luxS and Autoinducer-2 Production in Gut Bacteroidales"
id: "biorxiv-7-distribution-of-luxs-and-production-of-autoinducer-2-among-gut-bacteroidales"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-7-distribution-of-luxs-and-production-of-autoinducer-2-among-gut-bacteroidales"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1?rss=1"
published_at: "2026-07-27T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Distribution of luxS and Autoinducer-2 Production in Gut Bacteroidales
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-7-distribution-of-luxs-and-production-of-autoinducer-2-among-gut-bacteroidales
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1?rss=1)
- **Published At:** 2026-07-27T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study surveys the genomic distribution of **luxS** (part of the mtnN-luxS pathway) and **sahH** across Bacteroidota, with focused analysis on gut Bacteroidales. - Ancestral Bacteroidota likely encoded **sahH**, and multiple independent replacements by **mtnN-luxS** occurred during diversification. - In several lineages (Bacteroidaceae, Parabacteroides, many Prevotellaceae) **mtnN-luxS** or **sahH** occupy the same genomic neighborhood adjacent to yfhO. - Experimental work used Bacteroides fragilis (contains **sahH**), Bacteroides uniformis and Phocaeicola vulgatus (contain **mtnN-luxS**) to test AI-2 production and response. - Strains encoding **luxS** produced **autoinducer-2 (AI-2)**, demonstrating active AI-2 generation by **mtnN-luxS**-containing gut Bacteroidales. - Transcriptomics and gnotobiotic mouse experiments with wild-type strains and genetic swaps between **mtnN-luxS** and **sahH** indicated that Bacteroidaceae species tested did not respond to AI-2 under the experimental conditions. - Metagenomic analyses of 15 human gut datasets show that **mtnN-luxS**-containing Bacteroidales species represent on average between approximately 5.1% and 33% of total bacteria in these datasets, implying substantial community-level AI-2 production that could be sensed by other responsive microbes. - The manuscript is a preprint and has not undergone peer review; specific experimental details beyond the abstract are not reported in the provided source.
## Clinical Analysis & Structured Key Points
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Nolan Warren Kennedy 1 Northwestern University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Nolan%2BWarren%2BKennedy%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Kennedy%20NW&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANolan%2BWarren%2BKennedy%2B) Rebecca Gellman 2 The University of Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Rebecca%2BGellman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gellman%20R&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARebecca%2BGellman%2B) Michael J Coyne 2 The University of Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Michael%2BJ%2BCoyne%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Coyne%20MJ&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMichael%2BJ%2BCoyne%2B) Jessica Little 2 The University of Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jessica%2BLittle%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Little%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJessica%2BLittle%2B) Ashley M Sidebottom 2 The University of Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ashley%2BM%2BSidebottom%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sidebottom%20AM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAshley%2BM%2BSidebottom%2B) Laurie Comstock 2 The University of Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Laurie%2BComstock%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Comstock%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALaurie%2BComstock%2B) * [ORCID record for Laurie Comstock](http://orcid.org/0009-0002-6368-8351 "Open in new tab") * For correspondence: lecomstock@uchicago.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5658653/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5658653/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5658653/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.07.27.740950v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5658653/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract One of the best studied quorum sensing (QS) molecules, autoinducer-2 (AI-2), regulates processes in numerous bacteria. LuxS is an enzyme of the activated methyl cycle which, along with MtnN, converts S-adenosyl-homocysteine to homocysteine, releasing DPD (4,5-dihydroxy-2,3-pentanedione) which is spontaneously converted to AI-2. Many bacteria do not encode MtnN-LuxS and instead encode SahH, which directly converts S-adenosyl-homocysteine to homocysteine without AI-2 production. The genomes of some gut Bacteroidales were shown to contain luxS, however, these reports, as well as reports of the production of AI-2 by gut Bactereoidales have been inconsistent. We performed a comprehensive analysis of the distribution of luxS and sahH in Bacteroidota with an in-depth exploration of gut Bacteroidales. The data suggest that the ancestral Bacteroidota contained sahH, with numerous independent replacements with mtnN-luxS during diversification. In Bacteroidaceae, Parabacteroides, and many Prevotellaceae, mtnN-luxS or sahH are present in the same genetic region, adjacent to yfhO. Using Bacteroides fragilis, which contains sahH, and Bacteroides uniformis and Phocaeicola vulgatus, whose genomes contain mtnN-luxS, we show that luxS-containing strains produce AI-2. Transcriptomic analyses and gnotobiotic mouse experiments using wild-type strains and mtnN-luxS and sahH genetic swaps showed that Bacteroidaceae species do not respond to AI-2 under the conditions tested. However, analyses of 15 human gut metagenomic datasets show that mtnN-luxS containing Bacteroidales species average between 5.1 – 33% of the total bacteria in these various human gut microbiome datasets, and therefore, likely produce substantial amounts of AI-2 sensed by responsive gut symbionts and pathogens. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-ND 4.0 International license](http://creativecommons.org/licenses/by-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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