Gut microbiota metabolic pathways: Key players in knee osteoarthritis development.
Exp Gerontol
; 196: 112566, 2024 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-39226947
ABSTRACT
OBJECTIVE:
To confirm the causality of gut microbiota pathway abundance and knee osteoarthritis (KOA).METHODS:
Microbial metabolic pathways were taken as exposures, with data from the Dutch Microbiome Project (DMP). Data on KOA from the UK Biobank were utilized as endpoints. In addition, we extracted significant and independent single nucleotide polymorphisms as instrumental variables. Two-sample Mendelian randomization (MR) analysis was applied to explore the causal relationship between gut microbiota pathway abundance and KOA, and MR-Egger and weighted median were used as additional validation of the MR results. Meanwhile, Cochran Q, MR-Egger intercept, MR-PRESSO, and leave-one-out were used to perform sensitivity analyses on the MR results.RESULTS:
MR results showed that enterobactin biosynthesis, diacylglycerol biosynthesis I, Clostridium acetobutylicum acidogenic fermentation, glyoxylate bypass and tricarboxylic acid cycle were the risk factors for KOA. (OR = 1.13,95%CI = 1.04-1.23;OR = 1.12,95%CI = 1.04-1.20;OR = 1.14,95%CI = 1.04-1.26; OR = 1.06,95%CI = 1.00-1.12) However, adenosylcobalamin salvage from cobinamide I, hexitol fermentation to lactate formate ethanol and acetate, purine nucleotides degradation II aerobic, L tryptophan biosynthesis and inosine 5 phosphate biosynthesis III pathway showed significant protection against KOA. (OR = 0.93,95%CI = 0.86-1.00;OR = 0.94,95%CI = 0.88-1.00;OR = 0.91,95%CI = 0.86-0.97;OR = 0.95,95%CI = 0.92-0.99; OR = 0.91, 95%CI = 0.85-0.98) Further multiplicity and sensitivity analyses demonstrated the robustness of the results.CONCLUSION:
Our study identified specific metabolic pathways in gut microbiota that promote or inhibit KOA, which provides the most substantial evidence-based medical evidence for the pathogenesis and prevention of KOA.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoarthritis, Knee
/
Mendelian Randomization Analysis
/
Gastrointestinal Microbiome
Limits:
Humans
Language:
En
Journal:
Exp Gerontol
/
Exp. gerontol
/
Experimental gerontology
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom