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Relevance of protein fermentation to gut health
Abstract
It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized.
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“Studies in animal models and in vitro show that compounds like ammonia, phenols, p-cresol, certain amines and hydrogen sulfide, play important roles in the initiation or progression of a leaky gut, inflammation, DNA damage and cancer progression.15”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [15]
In the citing paper
“Regarding this, as protein consumption is increased, the amount of proteins reaching the colon is increasing correspondingly, leading to numerous and diverse bacterial metabolite production (e.g., hydrogen sulfide, branched-chain fatty acids (BCFAs), SCFAs, polyamines, ammonia, methane, aromatic compounds, nitric oxide, tyramine, tryptamine, phenethylamine, serotonin, histamine, and others) in the”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [147]
In the citing paper
“BCAA deamination leading to BCFA production is a marker of colonic fermentation developed by protein consumption [147].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [147]
In the citing paper
“Fermented foods enriched with Lactobacillus sp. and Bifidobacteria sp [129] can result in specific changes in gut microbiota activity, improving stress-induced symptoms such as depression, mood disturbance as well as digestive issues [130].”
From Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes (2016) · cites this paper as [129]
In the citing paper
“While athletes may require a higher protein intake, high protein diets can affect the microbiota composition and function through amino acid fermentation in the colon that produces undesirable metabolites (e.g. phenol, hydrogen sulfide and amines) and urea and tend to lead to higher fecal pH (reviewed by Windey et al [129]).”
From Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes (2016) · cites this paper as [129]
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“88 128 129 Since fermentable carbohydrates are preferentially used over proteins by most bacteria in the distal small intestine and proximal colon, most fermentation of amino acids as an energy source occurs in the distal colon, where carbohydrates are depleted.”
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Di, T., Chen, G., Sun, Y., Ou, S., Zeng, X., & Ye, H. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2017.10.040 · Cited by 181
Singh, J., Metrani, R., Shivanagoudra, S. R., Jayaprakasha, G. K., & Patil, B. S. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b07306 · Cited by 187
Hydrogen cross-feeders of the human gastrointestinal tract
Smith, N. W., Shorten, P. R., Altermann, E., Roy, N. C., & McNabb, W. C. (2018) · Gut Microbes · doi:10.1080/19490976.2018.1546522 · Cited by 176
“Sulfate may also be generated from the breakdown of endogenous sulfurcontaining mucins.(49,50) However, SRB are unable to degrade these structures, so rely on other members of the microbiota to release free sulfate during their metabolism of mucins.”
BackgroundColorectal cancer occurrence and treatment based on changes in intestinal flora
Si, H., Yang, Q. F., Hu, H., Ding, C., Wang, H., & Lin, X. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.05.004 · Cited by 167
Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities
Pandey, H., Tang, D. W. T., Wong, S. H., & Lal, D. (2023) · Cancers · doi:10.3390/cancers15030866 · Cited by 171
Pillai, S. S., Gagnon, C. A., Foster, C., & Ashraf, A. P. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae499 · Cited by 180
Review of the association between meat consumption and risk of colorectal cancer
Kim, E., Coelho, D., & Blachier, F. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.07.018 · Cited by 156
“Phenolic and indolic compounds and BCFAs Phenolic and indolic compounds are produced from aromatic amino acids (tyrosine, tryptophan, and phenylalanine) during degradation by bacteria [17].”
BackgroundInfluentialStructural diversity, functional aspects and future therapeutic applications of human gut microbiome
Ghosh, S., & Pramanik, S. (2021) · Archives of Microbiology · doi:10.1007/s00203-021-02516-y · Cited by 158
The Pyromaniac Inside You: Salmonella Metabolism in the Host Gut
Rivera-Chávez, F., & Bäumler, A. J. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104108 · Cited by 149
Jiang, H., Chen, C., & Gao, J. (2022) · Nutrients · doi:10.3390/nu15010151 · Cited by 153
“The efficiency of protein fermentation in the distal intestine tract is higher than that in the proximal section [10,11].”
BackgroundCan We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?
Brahe, L. K., Astrup, A. V., & Larsen, L. H. (2016) · Advances in Nutrition · doi:10.3945/an.115.010587 · Cited by 147
“However, HP diets have been hypothesized to be harmful for colonic health because they lead to increased fermentation of undigested protein in the colon, which produces potential harmful metabolites, such as ammonia, phenols, hydrogen sulfide, and amines (71, 87, 88).”
BackgroundHeating Reduces Proso Millet Protein Digestibility via Formation of Hydrophobic Aggregates
Gulati, P., Li, A., Holding, D. R., Santra, D. K., Zhang, Y., & Rose, D. J. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b05574 · Cited by 144
Delzenne, N. M., Knudsen, C., Beaumont, M., Rodriguez, J., Neyrinck, A. M., & Bindels, L. B. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665118002756 · Cited by 146
Gut-Derived Protein-Bound Uremic Toxins
Graboski, A. L., & Redinbo, M. R. (2020) · Toxins · doi:10.3390/toxins12090590 · Cited by 137
A Review of the Role of the Gut Microbiome in Personalized Sports Nutrition
Hughes, R. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00191 · Cited by 143
Ferreira-Lazarte, Á., Moreno, F. J., Cueva, C., Gil‐Sánchez, I., & Villamiel, M. (2018) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2018.11.088 · Cited by 136
Diet, the intestinal microbiota, and immune health in aging
Clements, S. J., & Carding, S. R. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2016.1211086 · Cited by 163
“…elderly population, recommendations for protein intake should be considered carefully, since the US recommended daily amount (RDA) for adults is 0.8 g protein per kg weight regardless of age, although the elderly may benefit from a higher protein intake (Campbell et al., 2001; Wolfe et al., 2008).”
BackgroundInfluentialBlachier, F., Beaumont, M., Andriamihaja, M., Davila, A., Lan, A., Grauso, M., Armand, L., Benamouzig, R., & Tomé, D. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.11.015 · Cited by 131
“High-protein diets increase fecal concentrations of amino acidederived bacterial metabolites, such as branched-chain fatty acids, phenolic compounds, hydrogen sulfide, and ammonia.(10) Colonic luminal pH may also be modified by dietary changes.”
BackgroundDallas, D. C., Murray, N. M., & Gan, J. (2015) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-015-9334-3 · Cited by 129
“flammatory reactions [119, 120], provoke colonic epithelial cell DNA damage [121] and reduce colonic epithelial cell viability [122].”
BackgroundCowieson, A. J., & Roos, F. F. (2016) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2016.04.015 · Cited by 128
Vegetable-Based Diets for Chronic Kidney Disease? It Is Time to Reconsider
Cases, A., Cigarrán, S., Mas, S., & González‐Parra, E. (2019) · Nutrients · doi:10.3390/nu11061263 · Cited by 130
“In the absence of fermentable carbohydrates, protein fermentation induces the formation of potentially deleterious byproducts, such as sulfides, amines, ammonia, and phenols [24] that can accumulate in CKD and exert their harmful effects on the host [10].”
BackgroundKostovcikova, K., Coufal, S., Galanova, N., Fajstova, A., Hudcovic, T., Kostovcik, M., Prochazkova, P., Jiraskova Zakostelska, Z., Cermakova, M., Sediva, B., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00919 · Cited by 126
“In line with others (21, 22), our results are showing the later one is less digestible and thus available for further processing in the colon.”
BackgroundResultJäger, R., Zaragoza, J., Purpura, M., Iametti, S., Marengo, M., Tinsley, G. M., Anzalone, A. J., Oliver, J. M., Fiore, W., Biffi, A., et al. (2020) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-020-09656-5 · Cited by 134
Posttraumatic stress disorder: does the gut microbiome hold the key?
Leclercq, S., Forsythe, P., & Bienenstock, J. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716635535 · Cited by 121
“Conversely, digestion of proteins results in the production of potentially toxic metabolites such as phenolic and sulphur-containing compounds.(53) Intestinal epithelial cells exposed to phenol show, in a dose-dependent manner, an increase in paracellular permeability due to delocalization of the intercellular tight j…”
BackgroundGut dysbacteriosis and intestinal disease: mechanism and treatment
Meng, X., ZHANG, G., Cao, H., Yu, D., Fang, X., de Vos, W. M., & Wu, H. (2020) · Journal of Applied Microbiology · doi:10.1111/jam.14661 · Cited by 130
“Ammonia is also a carcinogen at low concentrations and has been shown to be associated with mucosal damage and colorectal adenocarcinoma in animal models (Windey et al. 2012).”
BackgroundBlachier, F., Beaumont, M., Portune, K. J., Steuer, N., Lan, A., Audebert, M., Khodorova, N., Andriamihaja, M., Airinei, G., Benamouzig, R., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.09.016 · Cited by 124
Vasquez, R., Oh, J. K., Song, J. H., & Kang, D. (2022) · Journal of Animal Science and Technology · doi:10.5187/jast.2022.e58 · Cited by 131
The role of key gut microbial metabolites in the development and treatment of cancer
Jaye, K. M., Li, C. G., Chang, D., & Bhuyan, D. J. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2038865 · Cited by 129
“Further evidence supporting this trend has led to the understanding that protein fermentation in the distal colon has detrimental effects on host health by producing toxic ammonia, amines, phenols and sulfides, in comparison to carbohydrate fermentation which generates health benefitting short-chain fatty acids (SCFAs…”
BackgroundKårlund, A., Gómez-Gallego, C., Turpeinen, A. M., Palo-oja, O.-M., El-Nezami, H. S., & Kolehmainen, M. (2019) · Nutrients · doi:10.3390/nu11040829 · Cited by 140
“The bacterial fermentation of dietary amino acids may result in end-products, such as ammonia, biogenic amines and indolic and phenolic compounds among others, having systemic and metabolic effects in the host [18], and possibly impacting immunomodulatory, neurological, cardiovascular, and gut functions [18,20,91].”
BackgroundDigestion of Protein in Premature and Term Infants
Dallas, D. C. (2012) · Journal of Nutritional Disorders & Therapy · doi:10.4172/2161-0509.1000112 · Cited by 120
“However, the long-term effects of exposure to these metabolites on the gut mucosa and epithelial cells remain unclear [14].”
BackgroundInfluentialThe Role of the Gut Microbiome on Chronic Kidney Disease
Sampaio‐Maia, B., Simões‐Silva, L., Pestana, M., Araújo, R., & Soares‐Silva, I. (2016) · Advances in applied microbiology · doi:10.1016/bs.aambs.2016.06.002 · Cited by 120
Microbiota in cancer development and treatment
Raza, M. H., Gul, K., Arshad, A., Riaz, N., Waheed, U., Rauf, A., Aldakheel, F. M., Alduraywish, S. A., Rehman, M. U., Abdullah, M., et al. (2018) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-018-2816-0 · Cited by 122
Review article: FODMAPS, prebiotics and gut health‐the FODMAP hypothesis revisited
Gibson, P. R., Halmos, E. P., & Muir, J. G. (2020) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15818 · Cited by 119
“A study ex vivo using fresh faecal slurries showed that FOS rapidly and potently inhibited hydrogen sulphide production even when stimulated by addition of cysteine to the slurry [68].”
BackgroundBile Acids and Cancer: Direct and Environmental-Dependent Effects
Ciaula, A. D., Wang, D. Q. ‐., Molina‐Molina, E., Baccetto, R., Calamita, G., Palmieri, V. O., & Portincasa, P. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5501 · Cited by 119
González, A., Nobre, C., Simões, L. S., Cruz, M., Loredo‐Treviño, A., Rodríguez‐Jasso, R. M., Contreras, J. C., Texeira, J. A., & Belmares, R. E. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.128884 · Cited by 117
Nielsen, D. S. G., Jensen, B. B., Theil, P. K., Nielsen, T. S., Knudsen, K. E. B., & Purup, S. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2017.10.023 · Cited by 115
Metadata
- Authors
- Windey, K., De Preter, V., & Verbeke, K.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Corresponding author
- Verbeke, Kristin
- ORCID
- Verbeke, Kristin
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2011-11-25
- Volume
- 56
- Issue
- 1
- Pages
- 184-196
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2101238009
- Cited by
- 692
- References
- 106
- Citations by year
- 2026: 57 · 2025: 56 · 2024: 59 · 2023: 70 · 2022: 60 · 2021: 59 · 2020: 75 · 2019: 52 · 2018: 53 · 2017: 40 · 2016: 41 · 2015: 26 · 2014: 19 · 2013: 18 · 2012: 6
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- protein fermentation, gut health, distal colon, short-chain fatty acids, ammonia, amines, phenols, sulfide, colorectal cancer, ulcerative colitis, meat consumption, heme, heterocyclic amines, dietary fat, colonic metabolites
- MeSH terms
- Ammonia, Animals, Colon, Cresols, Diet, Fermentation, Humans, Hydrogen Sulfide, Meat, Phenols, Proteins, Colorectal Neoplasms, Gastrointestinal Tract
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