Do High-protein Diets Have the Potential to Reduce Gut Barrier Function in a Sex-dependent Manner?

Overview

Journal Eur J Nutr

Specialty Nutritional Sciences

Date 2024 Apr 25

PMID 38662018

Authors

Daniel James

Carlos Poveda

Gemma E Walton

J Stephen Elmore

Brandon Linden

John Gibson

Bruce A Griffin

M Denise Robertson

Marie C Lewis

Affiliations

Soon will be listed here.

Abstract

Purpose: Impaired gut barrier function is associated with systemic inflammation and many chronic diseases. Undigested dietary proteins are fermented in the colon by the gut microbiota which produces nitrogenous metabolites shown to reduce barrier function in vitro. With growing evidence of sex-based differences in gut microbiotas, we determined whether there were sex by dietary protein interactions which could differentially impact barrier function via microbiota modification.

Methods: Fermentation systems were inoculated with faeces from healthy males (n = 5) and females (n = 5) and supplemented with 0.9 g of non-hydrolysed proteins sourced from whey, fish, milk, soya, egg, pea, or mycoprotein. Microbial populations were quantified using fluorescence in situ hybridisation with flow cytometry. Metabolite concentrations were analysed using gas chromatography, solid phase microextraction coupled with gas chromatography-mass spectrometry and ELISA.

Results: Increased protein availability resulted in increased proteolytic Bacteroides spp (p < 0.01) and Clostridium coccoides (p < 0.01), along with increased phenol (p < 0.01), p-cresol (p < 0.01), indole (p = 0.018) and ammonia (p < 0.01), varying by protein type. Counts of Clostridium cluster IX (p = 0.03) and concentration of p-cresol (p = 0.025) increased in males, while females produced more ammonia (p = 0.02), irrespective of protein type. Further, we observed significant sex-protein interactions affecting bacterial populations and metabolites (p < 0.005).

Conclusions: Our findings suggest that protein fermentation by the gut microbiota in vitro is influenced by both protein source and the donor's sex. Should these results be confirmed through human studies, they could have major implications for developing dietary recommendations tailored by sex to prevent chronic illnesses.

References

Barker H . Amino acid degradation by anaerobic bacteria. Annu Rev Biochem. 1981; 50:23-40. DOI: 10.1146/annurev.bi.50.070181.000323. View

Langendijk P, Schut F, Jansen G, Raangs G, Kamphuis G, Wilkinson M . Quantitative fluorescence in situ hybridization of Bifidobacterium spp. with genus-specific 16S rRNA-targeted probes and its application in fecal samples. Appl Environ Microbiol. 1995; 61(8):3069-75. PMC: 167584. DOI: 10.1128/aem.61.8.3069-3075.1995. View

Homma H, Hoy E, Xu D, Lu Q, Feinman R, Deitch E . The female intestine is more resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states. Am J Physiol Gastrointest Liver Physiol. 2004; 288(3):G466-72. DOI: 10.1152/ajpgi.00036.2004. View

An C, Kuda T, Yazaki T, Takahashi H, Kimura B . Caecal fermentation, putrefaction and microbiotas in rats fed milk casein, soy protein or fish meal. Appl Microbiol Biotechnol. 2013; 98(6):2779-87. DOI: 10.1007/s00253-013-5271-5. View

Rigottier-Gois L, Bourhis A, Gramet G, Rochet V, Dore J . Fluorescent hybridisation combined with flow cytometry and hybridisation of total RNA to analyse the composition of microbial communities in human faeces using 16S rRNA probes. FEMS Microbiol Ecol. 2009; 43(2):237-45. DOI: 10.1111/j.1574-6941.2003.tb01063.x. View

Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T . Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006; 72(2):1027-33. PMC: 1392899. DOI: 10.1128/AEM.72.2.1027-1033.2006. View

Coelho M, Monteyne A, Dunlop M, Harris H, Morrison D, Stephens F . Mycoprotein as a possible alternative source of dietary protein to support muscle and metabolic health. Nutr Rev. 2019; 78(6):486-497. DOI: 10.1093/nutrit/nuz077. View

Haro C, Rangel-Zuniga O, Alcala-Diaz J, Gomez-Delgado F, Perez-Martinez P, Delgado-Lista J . Intestinal Microbiota Is Influenced by Gender and Body Mass Index. PLoS One. 2016; 11(5):e0154090. PMC: 4881937. DOI: 10.1371/journal.pone.0154090. View

McKenna C, Salvador A, Hughes R, Scaroni S, Alamilla R, Askow A . Higher protein intake during resistance training does not potentiate strength, but modulates gut microbiota, in middle-aged adults: a randomized control trial. Am J Physiol Endocrinol Metab. 2021; 320(5):E900-E913. DOI: 10.1152/ajpendo.00574.2020. View

10.

Lim S, Page A, Li H, Carragher J, Searle I, Robertson S . Sexually Dimorphic Response of Increasing Dietary Intake of High Amylose Wheat on Metabolic and Reproductive Outcomes in Male and Female Mice. Nutrients. 2019; 12(1). PMC: 7019933. DOI: 10.3390/nu12010061. View

11.

Nelson K, Fleischmann R, DeBoy R, Paulsen I, Fouts D, Eisen J . Complete genome sequence of the oral pathogenic Bacterium porphyromonas gingivalis strain W83. J Bacteriol. 2003; 185(18):5591-601. PMC: 193775. DOI: 10.1128/JB.185.18.5591-5601.2003. View

12.

van der Giessen J, van der Woude C, Peppelenbosch M, Fuhler G . A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models. Cells. 2019; 8(3). PMC: 6468635. DOI: 10.3390/cells8030261. View

13.

Xiao L, Feng Q, Liang S, Sonne S, Xia Z, Qiu X . A catalog of the mouse gut metagenome. Nat Biotechnol. 2015; 33(10):1103-8. DOI: 10.1038/nbt.3353. View

14.

Bruewer M, Luegering A, Kucharzik T, Parkos C, Madara J, Hopkins A . Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol. 2003; 171(11):6164-72. DOI: 10.4049/jimmunol.171.11.6164. View

15.

Singh P, Manning S . Impact of age and sex on the composition and abundance of the intestinal microbiota in individuals with and without enteric infections. Ann Epidemiol. 2016; 26(5):380-5. PMC: 9494358. DOI: 10.1016/j.annepidem.2016.03.007. View

16.

Liu Y, Gibson G, Walton G . An In Vitro Approach to Study Effects of Prebiotics and Probiotics on the Faecal Microbiota and Selected Immune Parameters Relevant to the Elderly. PLoS One. 2016; 11(9):e0162604. PMC: 5017648. DOI: 10.1371/journal.pone.0162604. View

17.

Yokoo K, Yamamoto Y, Suzuki T . Ammonia impairs tight junction barriers by inducing mitochondrial dysfunction in Caco-2 cells. FASEB J. 2021; 35(11):e21854. DOI: 10.1096/fj.202100758R. View

18.

Frandsen E, Kjeldsen M, Kilian M . Inhibition of Prevotella and Capnocytophaga immunoglobulin A1 proteases by human serum. Clin Diagn Lab Immunol. 1997; 4(4):458-64. PMC: 170550. DOI: 10.1128/cdli.4.4.458-464.1997. View

19.

Franks A, Harmsen H, Raangs G, Jansen G, Schut F, Welling G . Variations of bacterial populations in human feces measured by fluorescent in situ hybridization with group-specific 16S rRNA-targeted oligonucleotide probes. Appl Environ Microbiol. 1998; 64(9):3336-45. PMC: 106730. DOI: 10.1128/AEM.64.9.3336-3345.1998. View

20.

Wang J, Ji H, Wang S, Liu H, Zhang W, Zhang D . Probiotic Promotes Intestinal Barrier Function by Strengthening the Epithelium and Modulating Gut Microbiota. Front Microbiol. 2018; 9:1953. PMC: 6117384. DOI: 10.3389/fmicb.2018.01953. View