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The fate of dietary protein in the gastrointestinal tract and implications for colonic disease

Nature Reviews Gastroenterology & Hepatology (2026)Cite this article

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Abstract

Protein is an essential nutrient in the human diet. Global Westernization and modern dietary trends have seen protein become a more substantial contributor to the Western diet, with dietary sources expanding beyond traditional wholefoods to a myriad of processed protein-enriched food products. Although dietary protein is critical for human health, it has also been implicated in colonic health and disease both directly via the microbial fermentation of protein entering the colonic environment and indirectly by affecting the intake of other nutrients in the diet such as fibre. Although protein digestion in the small intestine is highly efficient, there are numerous factors that can influence the capacity for protein digestion and absorption, particularly dietary factors representative of modern-day protein intakes such as high protein diets and food manufacturing. The subsequent fermentation of protein and production of microbial metabolites in the colon is in turn affected by the source of protein entering the colon and the presence of fibre. In this Review, we examine factors that influence human digestion and absorption of protein in the small intestine and protein fermentation in the colon, describing implications for colonic health and disease.

Key points

  • Global Westernization has changed the way protein is consumed in modern-day society with trends focused on high protein diets and processed protein sources.

  • Dietary and non-dietary factors including protein source, fibre intake and medications influence capacity for digestion and absorption of protein in the small intestine and subsequent availability for colonic fermentation.

  • Metabolites produced during colonic protein fermentation have the potential to exert beneficial and/or detrimental effects on the colonic mucosa.

  • Optimization of protein intake requires careful consideration of the effect of protein on colonic health directly via its colonic fermentation and indirectly by its effect on dietary intake of other nutrients.

  • Further research is required to personalize protein recommendations based on genetic, environmental and microbial data to optimize health and minimize the risk of colonic disease.

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Fig. 1: The fate of dietary protein in the human gastrointestinal tract.
Fig. 2: Trends in dietary protein intake and colonic disease since inception of Westernized dietary patterns.
Fig. 3: Production of metabolites from protein substrates by colonic microorganisms and their subsequent analysis in biological samples.
Fig. 4: Fermentation of dietary substrates across different sections of the colon.

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Acknowledgements

The authors acknowledge grant funding and academic support from The Hospital Research Foundation Group and Michelle McGrath Fellowship. The authors acknowledge A. Holasek from the Central Adelaide Local Health Network Library service who provided support with the practicalities of literature searching. The figures were originally developed with BioRender before being redrawn; Supplementary Fig 1 was created with BioRender; Mathias, R. (2025) https://BioRender.com/v5telb9.

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Authors and Affiliations

  1. School of Medicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia

    Rachel H. Davis, Robert V. Bryant & Alice S. Day

  2. Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia

    Rachel H. Davis, Robert V. Bryant & Alice S. Day

  3. Department of Gastroenterology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia

    Peter R. Gibson

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  1. Rachel H. Davis
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Contributions

All authors researched data for the article. R.H.D. wrote the original article and created tables and figures. All authors made substantial contributions to discussion of content. All authors reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Alice S. Day.

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Competing interests

R.V.B. has received grant, research support or speaker fees (all paid to his employer for research support) from AbbVie, Ferring, Janssen, Shire, Takeda, GSK and Emerge Health; and is a shareholder in Biomebank. P.R.G. is a consultant or advisory board member for Anatara, Atmo Biosciences, Topas and Comvita; has received research grants for investigator-driven studies from Mindset Health, and speaker honoraria from Dr Falk Pharma and Mindset Health Pty.; and is a shareholder in Atmo Biosciences. His salary is derived from sales of a digital application (Monash University FODMAP diet app), patient booklets cookbooks and online courses, all of which relate to the low FODMAP diet therapy. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Alan Mackie, Kaitlin Day and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Review criteria

The electronic databases Medline, Embase, Emcare and Cochrane Library were searched up to 18 November 2025 to retrieve articles. A comprehensive search strategy using both keywords and MeSH terms was developed to identify a broad scope of potentially relevant articles (Supplementary Table 5). Search terms and synonyms to signify ’Protein‘, ’Digestion‘, ’Absorption‘ and ’Fermentation‘ were used. No limits were applied to the search strategy. However, a range of synonyms for ’animals‘ and ’paediatrics‘ were used in attempt to refine the search to human adults. Citations from each database were exported into EndNote 20 and then Covidence where duplicates were removed. The resulting 8,331 articles were screened by title and abstract to locate primary studies and reviews detailing digestion, absorption or fermentation of protein in the human gastrointestinal tract. Studies in animals, in vitro or simulated digestion, and studies in infants and children were excluded. Additional papers including animal or in vitro data relevant to the concepts discussed in this paper were subsequently included. Full-text articles were screened to determine relevance for inclusion in this narrative review.

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Davis, R.H., Bryant, R.V., Gibson, P.R. et al. The fate of dietary protein in the gastrointestinal tract and implications for colonic disease. Nat Rev Gastroenterol Hepatol (2026). https://doi.org/10.1038/s41575-026-01173-0

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