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Long Term High Protein Diet Feeding Alters the Microbiome and Increases Intestinal Permeability, Systemic Inflammation and Kidney Injury in Mice
Author(s) -
Snelson Matthew,
Clarke Rachel Elise,
Nguyen TuongVi,
Penfold Sally Anne,
Forbes Josephine Maree,
Tan Sih Min,
Coughlan Melinda Therese
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000851
Subject(s) - occludin , inflammation , endocrinology , kidney , medicine , albuminuria , microbiome , intestinal permeability , systemic inflammation , blood urea nitrogen , biology , chemistry , biochemistry , tight junction , bioinformatics
Scope This study evaluates the effects of a chronic high protein diet (HPD) on kidney injury, intestinal permeability and gut microbiota perturbations in a mouse model. Method and results Mice are fed a diet containing either 20% or 52% energy from protein for 24 weeks; protein displaced an equivalent amount of wheat starch. The HPD does not alter glycemic control or body weight. The HPD induces kidney injury as evidenced by increase in albuminuria, urinary kidney injury molecule‐1, blood urea nitrogen, urinary isoprostanes and renal cortical NF‐κB p65 gene expression. HPD decreases intestinal occludin gene expression, increases plasma endotoxin and plasma monocyte chemoattractant protein‐1, indicating intestinal leakiness and systemic inflammation. Cecal microbial analysis reveals that HPD feeding does not alter alpha diversity; however, it does alter beta diversity, indicating an altered microbial community structure with HPD feeding. Predicted metagenome pathway analysis demonstrates a reduction in branched‐chain amino acid synthesis and an increase of the urea cycle with consumption of a HPD. Conclusion These results demonstrate that long term HPD consumption in mice causes albuminuria, systemic inflammation, increase in gastrointestinal permeability and is associated with gut microbiome remodeling with an increase in the urea cycle pathway, which may contribute to renal injury.