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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microbial Symbioses

This article is part of the Research TopicImpact of Diet on Gut Microbiome Regulation in Chronic Inflammation and Aging ProcessesView all articles

Yeast Protein Modulates Metabolites Derived from the Human Gut Microbiota of Older Male Adults ex vivo to Strengthen Gut Barrier Function and Reduce Inflammation

Provisionally accepted
Pieter  Van Den AbbeelePieter Van Den Abbeele1*Lam Dai  VuLam Dai Vu1Jonas  PoppeJonas Poppe1Ingmar  A.J. van HengelIngmar A.J. van Hengel1Aurélien  BaudotAurélien Baudot1Yan  ZhangYan Zhang2Zhixian  ChenZhixian Chen2Jun  YanJun Yan2
  • 1Cryptobiotix SA, Ghent, Belgium
  • 2Angel Yeast Co Ltd, Yichang, China

The final, formatted version of the article will be published soon.

Introduction The rising global demand for protein is accelerating interest in sustainable alternatives with health benefits. While glycans are well known for supporting gut health, the role of dietary proteins in promoting healthy aging via microbiome modulation is less understood. Yeast protein (YP) represents a sustainable, non-animal, hypoallergenic option. Methods Using the clinically predictive ex vivo SIFR® technology (Systemic Intestinal Fermentation Research), we examined how YP influences the microbiome of older human adults (50–65 years, n=6), comparing its effects to whey protein isolate (WPI) and soy protein isolate (SPI). Results At a dose equivalent to 40 g/day, all protein sources supported gut barrier integrity and reduced inflammation, reflected by decreased pro-inflammatory markers and increased IL-10. These benefits were linked to higher short-chain fatty acid (SCFA) production, mainly from Bacillota and Bacteroidota, including microbial markers associated with healthy aging. YP and SPI specifically restored butyrate-producing microbes and increased microbial diversity, which is linked to longevity. Untargeted metabolomics revealed numerous beneficial amino acid-derived metabolites, including indoles and polyamines, known to act through gut-organ axes to extend health span. Despite similar overall profiles, product-specific differences emerged: YP most strongly reinforced barrier integrity, produced the lowest gas levels (suggesting superior tolerability), and yielded the lowest trimethylamine N-oxide, a compound linked to increased mortality in older adults. Discussion Collectively, these findings highlight the potential of YP as a sustainable protein source that modulates the microbiome and metabolome, reduces inflammation, and reinforces gut barrier function, which are key mechanisms for preserving health span and mitigating age-related decline.

Keywords: healthy aging, Systemic intestinal fermentation research (SIFR), transepithelial electricalresistance (TEER), Short-chain fatty acid (SCFA), branched-chain fatty acids (bCFA), communitymodulation score (CMS), alternative proteins

Received: 02 Sep 2025; Accepted: 07 Nov 2025.

Copyright: © 2025 Van Den Abbeele, Vu, Poppe, van Hengel, Baudot, Zhang, Chen and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Pieter Van Den Abbeele, pieter.vandenabbeele@cryptobiotix.eu

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