Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein

Margaret Murray; Melinda T Coughlan; Anne Gibbon; Vinod Kumar; Francine Z Marques; Sophie Selby-Pham; Matthew Snelson; Kirill Tsyganov; Gary Williamson; Trent M Woodruff; Tong Wu; Louise E Bennett

doi:10.3389/fnut.2022.816749

Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein

Front Nutr. 2022 Mar 24:9:816749. doi: 10.3389/fnut.2022.816749. eCollection 2022.

Authors

Margaret Murray^{1

2}, Melinda T Coughlan^{3

4}, Anne Gibbon⁵, Vinod Kumar⁶, Francine Z Marques^{7

8}, Sophie Selby-Pham¹, Matthew Snelson³, Kirill Tsyganov^{7

9}, Gary Williamson², Trent M Woodruff⁶, Tong Wu¹, Louise E Bennett¹

Affiliations

¹ School of Chemistry, Monash University, Clayton, VIC, Australia.
² Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, VIC, Australia.
³ Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
⁴ Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
⁵ Monash Animal Research Platform, Monash University, Churchill, VIC, Australia.
⁶ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁷ Hypertension Research Laboratory, School of Biological Sciences, Monash University, Clayton, VIC, Australia.
⁸ Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
⁹ Bioinformatics Platform, Monash University, Clayton, VIC, Australia.

Abstract

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fermentation metabolites, and the biomarkers of health status in pigs as a model of human digestion and metabolism. Weanling pigs were fed with standard or resistant protein diets for 4 weeks. The resistant protein, approximately half as digestible as the standard protein, was designed to enter the colon for microbial fermentation. Fecal and blood samples were collected to assess the microbiome and circulating metabolites and biomarkers. The resistant protein diet group consumed less feed and grew to ~50% of the body mass of the standard diet group. The diets had unique effects on the fecal microbiome, as demonstrated by clustering in the principal coordinate analysis. There were 121 taxa that were significantly different between groups (adjusted-p < 0.05). Compared with control, plasma tri-methylamine-N-oxide, homocysteine, neopterin, and tyrosine were increased and plasma acetic acid was lowered following the resistant protein diet (all p < 0.05). Compared with control, estimated glomerular filtration rate (p < 0.01) and liver function marker aspartate aminotransferase (p < 0.05) were also lower following the resistant protein diet. A resistant protein diet shifted the composition of the fecal microbiome. The microbial fermentation of resistant protein affected the levels of circulating metabolites and the biomarkers of health status toward a profile indicative of increased inflammation and the risk of chronic kidney disease.

Keywords: inflammation; kidney function; metabolomics; microbiome; protein fermentation; resistant protein.