Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction

Abstract

The relationship between change of gut microbiota and host serum metabolomics associated with low protein diet (LPD) has been unraveled incompletely in CKD patients. Fecal 16S rRNA gene sequencing and serum metabolomics profiling were performed. We reported significant changes in the β-diversity of gut microbiota in CKD patients having LPD (CKD-LPD, n = 16). We identified 19 genera and 12 species with significant differences in their relative abundance among CKD-LPD patients compared to patients receiving normal protein diet (CKD-NPD, n = 27) or non-CKD controls (n = 34), respectively. CKD-LPD had a significant decrease in the abundance of many butyrate-producing bacteria (family Lachnospiraceae and Bacteroidaceae) associated with enrichment of functional module of butanoate metabolism, leading to concomitant reduction in serum levels of SCFA (acetic, heptanoic and nonanoic acid). A secondary bile acid, glyco λ-muricholic acid, was significantly increased in CKD-LPD patients. Serum levels of indoxyl sulfate and p-cresyl sulfate did not differ among groups. The relationship between abundances of microbes and metabolites remained significant in subset of resampling subjects of comparable characteristics. Enrichment of bacterial gene markers related to D-alanine, ketone bodies and glutathione metabolism was noted in CKD-LPD patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients.

Effects of Low Protein Diet on Modulating Gut Microbiota in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis of International Studies

“…Four of them were controlled trials [18][19][20][21] and one was prospective observational study [17]. For those studies having more than one nutritional therapy [18,20], only the LPD group rather than the VLPD or supplemented-LPD was selected as the intervention group for analysis.…”

“…Overall, 239 patients (109 patients receiving LPD and 130 patients with normal-protein diet, NPD) were pooled for analysis. Although four of five articles have reported changes of gut microbiota in patients undergoing dietary intervention; however, the descriptions of microbial phylogenetic taxonomy classification were inconsistent, including families, phyla, genera and species-levels information [18][19][20][21]. One article reported clustering analysis of gut microbiota rather than microbial taxonomic changes [17].…”

“…Although an association between LPD and changes of gut microbiota has been indicated, it is unclear if changes of microbiota induced by dietary protein restriction can have beneficial effects on the outcomes of CKD patients. Diverse studies have indicated changes of gut microbiota associated with dietary interventions [17][18][19][20][21]. Black et al did not find changes of composition and diversity of gut microbiota [17]; Lai et al have reported variations of relative abundances of gut microbiota at the family-levels [18]; Jiang et al described changes at the genus-level [19]; Di Lorio [20] and Wu et al [21] revealed alterations in all three taxonomic levels, including bacterial families, genera and species, in patients undergoing LPD compared to those receiving normal diet.…”

“…Diverse studies have indicated changes of gut microbiota associated with dietary interventions [17][18][19][20][21]. Black et al did not find changes of composition and diversity of gut microbiota [17]; Lai et al have reported variations of relative abundances of gut microbiota at the family-levels [18]; Jiang et al described changes at the genus-level [19]; Di Lorio [20] and Wu et al [21] revealed alterations in all three taxonomic levels, including bacterial families, genera and species, in patients undergoing LPD compared to those receiving normal diet. In addition to the modifications of microbiota in the gut of patients receiving LPD, the associated alterations of related surrogate indices of outcome, such as clinical, metabolomic and anthropometric parameters, have been described inconsistently in these studies.…”

Chronic Kidney Disease Cohort Studies: A Guide to Metabolome Analyses

“…This type of study design can be easily implemented, is rather cheap, and can be started at enrollment or any later time point during the course of a cohort study. Since the inference of causal relationships between exposure and outcome by a one-time measurement is not possible, these studies are traditionally used to investigate disease prevalence or the influence of environmental factors such as drugs, toxins, or diet, as, e.g., demonstrated in [ 42 ].…”