Among 59 calcium oxalate stone formers, microbial richness was significantly reduced compared to 60 healthy controls.
Calcium oxalate stone formers exhibited a marked depletion of short-chain fatty acid (SCFA)-producing bacteria, including Faecalibacterium prausnitzii and Eubacterium rectale.
This was linked to decreased fecal and plasma SCFA levels and reduced 24-hour urinary citrate.
Widespread metabolic disturbances were observed, particularly in tryptophan metabolism and the citrate cycle.
A positive correlation was found between plasma SCFA levels and urinary citrate excretion, indicating a regulatory link within the gut-kidney axis.
Mendelian randomization analysis suggested that Bacteroides thetaiotaomicron may be a potential microbial risk factor for stone formation.
In a hyperoxaluria rat model, interventions with F. prausnitzii, E. rectale, or sodium butyrate reduced renal calcium oxalate crystal deposition and kidney injury.
Simplified
BACKGROUND: The prevalence of calcium oxalate (CaOx) kidney stones is increasing, yet the underlying mechanisms remain incompletely understood. Emerging evidence suggests that gut microbiota-particularly short-chain fatty acid (SCFA)-producing bacteria-may modulate host metabolism and inflammation, thereby influencing stone formation. However, the mechanistic links between gut , metabolic disturbances, and CaOx stone pathophysiology remain to be fully elucidated. This study investigates gut microbiota composition, SCFA levels, and metabolomic alterations in CaOx stone formers (CSF), aiming to uncover potential pathophysiological mechanisms and therapeutic targets.
RESULTS: Among 59 CSF and 60 healthy controls (HC), CSF exhibited significantly reduced microbial richness, with marked depletion of SCFA-producing bacteria such as Faecalibacterium prausnitzii and Eubacterium rectale. This dysbiosis was associated with decreased fecal and plasma SCFA levels, reduced 24-h urinary citrate, and widespread metabolic disturbances, particularly in tryptophan metabolism and the citrate cycle. Plasma SCFA levels were positively correlated with urinary citrate excretion, suggesting a regulatory link within the gut-kidney axis. Mendelian randomization analysis suggested that Bacteroides thetaiotaomicron may be a potential microbial risk factor for stone formation (OR = 1.26, 95% CI: 1.03-1.54, p = 0.028). In a hyperoxaluria rat model, interventions with F. prausnitzii, E. rectale, or sodium butyrate reduced renal CaOx crystal deposition and kidney injury.
CONCLUSIONS: Our findings highlight the central role of SCFA-producing bacteria and their metabolites in maintaining metabolic balance and protecting against CaOx stone formation. Gut dysbiosis and reduced SCFA levels appear to drive metabolic changes that contribute to stone development. B. thetaiotaomicron may increase stone risk, while F. prausnitzii, E. rectale, and sodium butyrate show therapeutic potential. These insights support further exploration of microbiome-based strategies for the prevention and personalized management of kidney stones. Video Abstract.
Key numbers
14 of 20 species
Decrease in SCFA-producing bacteria
Number of significantly depleted SCFA-producing species in CSF vs. HC.
1.26
Increased risk factor for stone formation
Odds ratio for Bacteroides thetaiotaomicron as a microbial risk factor.
24-h urinary citrate
Correlation with urinary citrate
Plasma SCFA levels positively correlate with urinary citrate excretion.
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Declarations. Ethics approval and consent to participate: The protocol for the population-based study was approved by the Guangxi Medical University Medical Research Ethics Committee (Approval No. 20220107). Informed consent was obtained from all participants, and the consent forms have been archived. Animal studies were conducted in accordance with ethical guidelines and experimental protocols approved by the Guangxi Medical University Medical Research Ethics Committee (Protocol No. 20220107). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
PubMed
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