Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease

Abstract

BackgroundThe relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease is unknown.MethodsWe conducted a case-control study of 88 individuals aged 4–18 years, which included 44 individuals with kidney stones containing ≥50% calcium oxalate and 44 controls matched for age, sex, and race. Shotgun metagenomic sequencing and untargeted metabolomics were performed on stool samples.ResultsParticipants who were kidney stone formers had a significantly less diverse gut microbiome compared with controls. Among bacterial taxa with a prevalence >0.1%, 31 taxa were less abundant among individuals with nephrolithiasis. These included seven taxa that produce butyrate and three taxa that degrade oxalate. The lower abundance of these bacteria was reflected in decreased abundance of the gene encoding butyryl-coA dehydrogenase (P=0.02). The relative abundance of these bacteria was correlated with the levels of 18 fecal metabolites, and levels of these metabolites differed in individuals with kidney stones compared with controls. The oxalate-degrading bacterial taxa identified as decreased in those who were kidney stone formers were components of a larger abundance correlation network that included Eggerthella lenta and several Lactobacillus species. The microbial (α) diversity was associated with age of stone onset, first decreasing and then increasing with age. For the individuals who were stone formers, we found the lowest α diversity among individuals who first formed stones at age 9–14 years, whereas controls displayed no age-related differences in diversity.ConclusionsLoss of gut bacteria, particularly loss of those that produce butyrate and degrade oxalate, associates with perturbations of the metabolome that may be upstream determinants of early-onset calcium oxalate kidney stone disease.

Composition of urinary stones in children: clinical and metabolic determinants in a French tertiary care center

“…Although in uenced by food intake, oxalate urinary excretion is particularly affected by intestinal oxalate absorption that is increased with digestive in ammation (26). Additionally, the gut microbiome is less diverse in pediatric calcium oxalate-stone formers, with particularly low levels of oxalate-degrading bacteria (7). Alterations of the microbiome diversity could explain the association found between frequent use of antibiotics and stone disease (27).…”

“…in the vitamin D, calcium, and phosphate metabolic pathways) (6). Recent papers have also suggested that intestinal absorption of stone promoters is in uenced by the microbiome diversity (7). In parallel, progress in the management of urinary tract infections (UTI) have led to a decreased frequency of infectious stones (8).…”

New Insights from Metabolomics in Pediatric Renal Diseases

“…Lithiasis is a disease with high prevalence and recurrence rates [ 85 ], in which metabolic perturbations lead to stone formation in the kidney (nephrolithiasis) or in the urinary tract (urolithiasis), resulting in various clinical manifestations including pain, dysuria, loss of kidney function, decreased bone mineral density, and cardiovascular disease in case of chronic conditions [ 86 ]. In the recent years, advances in the knowledge of the role of metabolism in the development and progression of this condition have been reported [ 87 ].…”

Microbiocenoses and the State of Local Mucosal Immunity of the Oral Cavity of Children and Adolescents with Liver Diseases

“…В останні роки багатьма дослідниками було виявлено, що у хворих з коморбідною патологією відбуваються суттєві зміни в імунній системі організму, що у подальшому і провокує розвиток патологічних процесів у ПР, які призводять до ще більших імунологічних зрушень. Тобто, наявність в анамнезі загальносоматичної патології істотно знижує захисні властивості організму, сприяючи негативному впливу на тканини пародонту і СОПР [5,6,7].…”