---
title: "Stool chemistry plus metagenomics identifies distinct adult gut health profiles"
id: "biorxiv-6-integrating-stool-chemistry-measurements-with-metagenomics-in-adults-reveals"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-6-integrating-stool-chemistry-measurements-with-metagenomics-in-adults-reveals"
content_type: "clinical_feed_article"
specialty: "Gastroenterology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Stool chemistry plus metagenomics identifies distinct adult gut health profiles
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-6-integrating-stool-chemistry-measurements-with-metagenomics-in-adults-reveals
- **Specialty:** [Gastroenterology](https://medichelpline.com/clinical-feed/gastroenterology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The investigators analyzed 877 adult stool samples with paired **shotgun metagenomics** and 12 stool chemistry metrics, integrating microbial taxonomic and functional profiles with host-derived measures. - **Calprotectin**, lactoferrin, and **secretory IgA** correlated with shifts in microbiome composition (beta diversity), indicating inflammatory markers map to compositional differences rather than richness alone. - Deviations in **short-chain fatty acids (SCFAs)**, including **butyrate**, were associated with changes in both alpha diversity and beta diversity, suggesting SCFA levels relate to overall diversity as well as community structure. - Network analysis produced two discrete microbial neighborhoods: one linked to higher **butyrate** and lower **calprotectin**/lactoferrin, the other to lower **butyrate** and higher inflammatory markers, implying opposing community states. - Machine learning models trained on taxonomic and functional features achieved modest accuracy in discriminating stool chemistry states; models performed best for SCFA deficiency and worse for host-derived inflammation metrics. - The study provides a systematic paired dataset framework for interpreting stool chemistry alongside metagenomics, but the source did not report methodological details such as assay platforms, exact model metrics, or specific limitations and next regulatory milestones.
## Clinical Analysis & Structured Key Points
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Timothy J Straub 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Timothy%2BJ%2BStraub%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Straub%20TJ&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATimothy%2BJ%2BStraub%2B) * [ORCID record for Timothy J Straub](http://orcid.org/0000-0001-5009-0778 "Open in new tab") Pamela A Nieto 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Pamela%2BA%2BNieto%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Nieto%20PA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3APamela%2BA%2BNieto%2B) * [ORCID record for Pamela A Nieto](http://orcid.org/0009-0003-2157-0272 "Open in new tab") Julian M Trachsel 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Julian%2BM%2BTrachsel%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Trachsel%20JM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJulian%2BM%2BTrachsel%2B) * [ORCID record for Julian M Trachsel](http://orcid.org/0000-0003-2357-7737 "Open in new tab") Hannah Sturgeon 2 Seeding Inc, Doing Business as TinyHealth; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Hannah%2BSturgeon%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sturgeon%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHannah%2BSturgeon%2B) * [ORCID record for Hannah Sturgeon](http://orcid.org/0000-0002-8265-9364 "Open in new tab") Star Edwards 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Star%2BEdwards%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Edwards%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AStar%2BEdwards%2B) Emeran A Mayer 3 University of California, Los Angeles, CA, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Emeran%2BA%2BMayer%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mayer%20EA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEmeran%2BA%2BMayer%2B) * [ORCID record for Emeran A Mayer](http://orcid.org/0000-0003-3923-3349 "Open in new tab") Ruben AT Mars 4 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ruben%2BAT%2BMars%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mars%20RA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARuben%2BAT%2BMars%2B) * [ORCID record for Ruben AT Mars](http://orcid.org/0000-0002-3917-9517 "Open in new tab") Kimberley V Sukhum 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Kimberley%2BV%2BSukhum%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sukhum%20KV&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKimberley%2BV%2BSukhum%2B) * For correspondence: kimberley@tinyhealth.com Cheryl S Hoy 1 Seeding Inc, doing business as Tiny Health, Austin, Texas, USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Cheryl%2BS%2BHoy%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hoy%20CS&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACheryl%2BS%2BHoy%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5901226/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5901226/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5901226/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5901226/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5901226/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Stool chemistry metrics, including calprotectin, lactoferrin, and secretory IgA, are used to assess gut inflammation in clinical or research settings. However, these measures in isolation provide a limited view of gut physiology and lack microbial context. Shotgun metagenomics offers a comprehensive assessment of the gut microbiome's taxonomic composition and functional potential, yet its integration with stool chemistry metrics remains underexplored. We analyzed 877 adult stool samples with paired shotgun metagenomic sequencing and chemistry measurements to integrate the microbiome with 12 stool chemistry metrics. Calprotectin, lactoferrin, and secretory IgA were associated with shifts in microbiome composition (beta diversity), while deviations from typical levels of short-chain fatty acids (SCFAs), including butyrate, were associated with both changes in alpha diversity and microbiome composition. Network analysis revealed two distinct microbial neighborhoods: one associated with higher butyrate and lower calprotectin and lactoferrin and another associated with lower butyrate and higher calprotectin and lactoferrin. Machine learning models trained on taxonomic and functional data showed modest discrimination of stool chemistry states, performing best for SCFA deficiency and less well for host-derived inflammatory metrics. Together, these findings systematically characterize microbiome-stool chemistry relationships across a large paired dataset, providing a framework for interpreting stool chemistry metrics in the context of shotgun metagenomic profiles. ### Competing Interest Statement TJS, PAN, JMT, HS, SE, and KVS are employees of Tiny Health and hold stock options in the company. KVS and SE have received compensation from Tiny Health to attend meetings. KVS has planned and pending patents related to the research. EAM serves as a medical advisor to Tiny Health and is a member of the scientific advisory boards of Axial Biotherapeutics, Pendulum, Bloom Science, Melius Microbiomics, APC Ireland, Ginger, Salvo, Seed, and EatWell. RAM is a founding advisor to Tiny Health, a role approved by the Medical-Industry Relations Committee of Mayo Clinic, fully independent of his employment at Mayo Clinic. CSH is the CEO and founder of Tiny Health. ## Funder Information Declared This study was financed and sponsored by Seeding, Inc. doing business as Tiny Health. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 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. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1?rss=1#page) [ Previous](https://www.biorxiv.org/content/10.64898/2026.10.20.760347v1 "Fine-Grained and Reliable Cell Classification from Pathology Images")[Next ](https://www.biorxiv.org/content/10.64898/2026.10.23.761066v1 "Sequence architecture of RNA reveals key molecular signatures driving RNA phase separation") Posted October 24, 2026. [ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.23.759375v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/24/2026.10.23.759375.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/10.64898/2026.10.23.759375v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Integrating stool chemistry measurements with metagenomics in adults reveals distinct gut health profiles Timothy J Straub, Pamela A Nieto, Julian M Trachsel, Hannah Sturgeon, Star Edwards, Emeran A Mayer, Ruben AT Mars, Kimberley V Sukhum, Cheryl S Hoy bioRxiv 2026.10.23.759375; doi: https://doi.org/10.64898/2026.10.23.759375 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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