---
title: "Housing Facility Differences in the Gut Microbiome Confound Arsenic Effects on Glucose Homeostasis"
id: "biorxiv-1-home-is-where-the-heterogeneity-is-housing-facility-level-differences-in-the"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-1-home-is-where-the-heterogeneity-is-housing-facility-level-differences-in-the"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1?rss=1"
published_at: "2026-08-03T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Housing Facility Differences in the Gut Microbiome Confound Arsenic Effects on Glucose Homeostasis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-1-home-is-where-the-heterogeneity-is-housing-facility-level-differences-in-the
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1?rss=1)
- **Published At:** 2026-08-03T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Inorganic arsenic (iAs) exposure has been linked to impaired glucose homeostasis and type 2 diabetes, but reported effects vary across studies and populations. The gut microbiome can both be affected by arsenic and modulate arsenic toxicity. - The study conducted parallel 50 ppm iAs drinking-water exposures in male C57BL/6J mice at two separate animal housing facilities to evaluate whether baseline microbial communities influence metabolic outcomes. - Hepatic arsenic measurements confirmed comparable iAs exposure at both sites, indicating exposure dose alone did not explain outcome differences. - Across multiple data layers (microbiome, bile acids, polar metabolites, untargeted metabolomics), the housing **facility** explained more variance than the iAs **treatment** group, accounting for 19–26% of variance in ordinations. - Baseline microbial communities and metabolic phenotypes differed between institutions; these baseline differences altered the direction and magnitude of iAs treatment effects on metabolism. - iAs exposure impaired **glucose clearance** at one facility while trending toward improvement at the other, demonstrating opposing metabolic responses under identical genetics and exposure. - A random forest classifier using 22 microbial species identified the housing facility with 96% cross-validated accuracy; classification by treatment never exceeded 67% accuracy. - Functional metagenomic analysis found ~11,733 genes (63% of detected genes) differentially abundant between facilities, whereas only 139 genes differed with iAs treatment. - The findings imply that pre-exposure **gut microbiome** and metabolome profiles are critical to understanding susceptibility to arsenic-induced metabolic dysfunction and suggest baseline characterization could help identify at-risk individuals or mitigation strategies. - Details such as sample sizes, exact metabolite identities, and specific statistical values beyond those reported were not provided in the source.
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Judy Malas 1 Department of Biological Sciences, University of Illinois at Chicago; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Judy%2BMalas%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Malas%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJudy%2BMalas%2B) * [ORCID record for Judy Malas](http://orcid.org/0009-0006-7150-1621 "Open in new tab") Lidan Zhao 2 Division of Endocrinology, Diabetes, and Metabolism; Department of Medicine; University of Illinois Chicago; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Lidan%2BZhao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zhao%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALidan%2BZhao%2B) Michael Landeche 3 Office of Animal Care and Institutional Biosafety, University of Illinois Chicago; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Michael%2BLandeche%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Landeche%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMichael%2BLandeche%2B) Ashley M Sidebottom 4 Host-Microbiome Metabolomics Facility, Duchossois Family Institute, 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) Jessica Little 5 Host-Microbiome Metabolomics Facility, Duchossois Family Institute, 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) Jarrad Hampton-Marcell 6 Department of Biological Sciences, University of Illinois Chicago * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jarrad%2BHampton-Marcell%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hampton-Marcell%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJarrad%2BHampton-Marcell%2B) * [ORCID record for Jarrad Hampton-Marcell](http://orcid.org/0000-0003-1982-4416 "Open in new tab") Robert M Sargis 2 Division of Endocrinology, Diabetes, and Metabolism; Department of Medicine; University of Illinois Chicago; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Robert%2BM%2BSargis%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sargis%20RM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARobert%2BM%2BSargis%2B) * [ORCID record for Robert M Sargis](http://orcid.org/0000-0001-7061-2983 "Open in new tab") * For correspondence: rsargis@uic.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5676925/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5676925/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5676925/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5676925/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5676925/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Inorganic arsenic (iAs) exposure is linked to impaired glucose homeostasis and type 2 diabetes, yet the magnitude and direction of reported effects vary substantially across studies and populations. The gut microbiome is both a target and a mediator of arsenic toxicity, suggesting that pre-exposure community composition may modulate the development of metabolic dysfunction. To test this, we conducted parallel 50 ppm iAs drinking-water exposures in male C57BL/6J mice at two animal facilities. Results were compared across facilities for metabolic phenotypes, hepatic arsenic levels, targeted and untargeted metabolomics, and shotgun metagenomics. Hepatic arsenic confirmed comparable exposure at both sites; however, the housing facility explained more variance than the iAs treatment group across every data layer. Baseline microbial communities and metabolic phenotypes at each institution differed, and this difference propagated into the iAs treatment effect. Critically, iAs exposure impaired glucose clearance at one site while trending toward improvement at the other. Facility explained 19 to 26% of variance in microbiome, bile acid, polar, and untargeted metabolite ordinations, while iAs treatment did not reach significance. A random forest classifier identified the facility with 96% cross-validated accuracy from 22 microbial species, whereas treatment classification did not exceed 67% accuracy. Functional metagenomic analyses revealed nearly 11,733 (63%) of genes were differentially abundant between facilities compared 139 with iAs treatment. Our results indicate that identical genetics and exposure may produce differential metabolic outcomes on different microbial backgrounds. Characterizing the baseline microbiome and metabolome is therefore critical both for identifying which individuals are most susceptible to the metabolic effects of arsenic exposure and for potentially reducing the risk of exposure through modulation of the gut microbiome. ### Competing Interest Statement RMS declares that he has received honoraria from CVS/Health unrelated to this work. All other authors declare no competing interests. ## Funder Information Declared National Institutes of Health, https://ror.org/01cwqze88, P30 ES027792, R01 ES028879, R21 ES030884 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 4.0 International license](http://creativecommons.org/licenses/by/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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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/08/03/2026.08.03.742222.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.08.03.742222v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Home is Where the Heterogeneity Is: Housing Facility-level Differences in the Gut Microbiome and Metabolic Phenotype Confound Arsenic Effects on Glucose Homeostasis in Male Mice Judy Malas, Lidan Zhao, Michael Landeche, Ashley M Sidebottom, Jessica Little, Jarrad Hampton-Marcell, Robert M Sargis bioRxiv 2026.08.03.742222; doi: https://doi.org/10.64898/2026.08.03.742222 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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