# Yeast protein modulates metabolites derived from the human gut microbiota of older male adults ex vivo to strengthen gut barrier function and reduce inflammation

## TL;DR

Yeast protein supports gut health in older adults by boosting beneficial microbes and reducing inflammation, similar to soy and whey proteins.

## Contribution

Yeast protein is shown to modulate the gut microbiome and metabolome in a way that supports healthy aging in older adults.

## Key findings

- Yeast protein reinforced gut barrier integrity and reduced inflammation more effectively than soy and whey proteins.
- Yeast protein increased microbial diversity and butyrate-producing microbes, which are linked to longevity.
- Yeast protein produced lower levels of trimethylamine N-oxide, a compound associated with higher mortality in older adults.

## Abstract

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.

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).

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.

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.

Yeast, soy and whey proteins exerted prebiotic effects ex vivo, strengthening the gut barrier and reducing inflammation, highlighting their potential to support healthy ageing.Graphic titled “Proteins with prebiotic effect, supporting healthy ageing.” It shows an ex vivo study of the gut-mediated health effects of proteins derived from yeast, soy or whey on subjects aged fifty to sixty-five. Partially digested proteins can impact the gut microbiome, metabolome and host health. The test products stimulated health-related metabolites like polyamines, SCFAs and indoles, while bacterial diversity increased. Health benefits within the gut include strengtened gut barrier and reduced inflammation. The induced shifts in microbiome composition and metabolism are even linked to healthy aging effects beyond the gut.

Yeast, soy and whey proteins exerted prebiotic effects ex vivo, strengthening the gut barrier and reducing inflammation, highlighting their potential to support healthy ageing.