Long Term High Protein Diet Feeding Alters the Microbiome and Increases Intestinal Permeability, Systemic Inflammation and Kidney Injury in Mice.

Abstract

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.

• Authors: Matthew Snelson, Rachel Elise Clarke, Tuong-Vi Nguyen, Sally Anne Penfold, Josephine Maree Forbes, Sih Min Tan, Melinda Therese Coughlan
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 8 Pg. e2000851 (04 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 33547877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2

Topics

• Acute Kidney Injury (etiology, microbiology, pathology)
• Albuminuria (etiology)
• Animals
• Body Weight
• Chemokine CCL2 (blood)
• Diet, High-Protein (adverse effects)
• Fibrosis
• Gastrointestinal Microbiome (genetics, physiology)
• Gene Expression
• Inflammation (etiology, microbiology)
• Intestines (physiology)
• Kidney (pathology)
• Male
• Mice, Inbred C57BL
• Permeability