TY - JOUR
T1 - Understanding the gut-kidney axis in nephrolithiasis: An analysis of the gut microbiota composition and functionality of stone formers
AU - Ticinesi, Andrea
AU - Milani, Christian
AU - Guerra, Angela
AU - Allegri, Franca
AU - Lauretani, Fulvio
AU - Nouvenne, Antonio
AU - Mancabelli, Leonardo
AU - Lugli, Gabriele Andrea
AU - Turroni, Francesca
AU - Duranti, Sabrina
AU - Mangifesta, Marta
AU - Viappiani, Alice
AU - Ferrario, Chiara
AU - Dodi, Rossella
AU - Dall'Asta, Margherita
AU - Del Rio, Daniele
AU - Ventura, Marco
AU - Meschi, Tiziana
PY - 2018
Y1 - 2018
N2 - Objectives: The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. Design: Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. Results: SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r= '0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r= '0.85, p=0.02). Conclusions: Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.
AB - Objectives: The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. Design: Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. Results: SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r= '0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r= '0.85, p=0.02). Conclusions: Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.
KW - diet
KW - kidney stones
KW - metagenomics
KW - microbiome
KW - oxalate
KW - urolithiasis
KW - diet
KW - kidney stones
KW - metagenomics
KW - microbiome
KW - oxalate
KW - urolithiasis
UR - http://hdl.handle.net/10807/163878
U2 - 10.1136/gutjnl-2017-315734
DO - 10.1136/gutjnl-2017-315734
M3 - Article
SN - 0017-5749
VL - 67
SP - 2097
EP - 2106
JO - Gut
JF - Gut
ER -