The Causal Effect of Gut Microbiota on the Development of Idiopathic Normal Pressure Hydrocephalus

Older people are particularly at risk for idiopathic normal pressure hydrocephalus (iNPH), a rare neurological condition without known risk factors. Several recent observational studies have reported that gut microbiota composition is associated with iNPH. However, the causal impact of gut microbiota on iNPH is unknown.

Single nucleotide polymorphisms strongly associated with 196 gut microbiota (18,340 individuals) were selected as instrumental factors, and the results were iNPH data (322 cases of iNPH and 21,043 controls). Random effects, inverse variance weighting, weighted medians, and Mendelian random (MR) -Egger were used to investigate causal effects. The Cochran's Q test, funnel plot, leave-one-out analysis, MR-Egger intercept test, and outlier (Global) test were employed in the sensitivity analysis to identify and compensate for the presence of pleiotropy. The MR-Steiger test also examined the hypothesised connection between exposure and result.

Our findings are mainly based on the inverse variance weighting approach and support a causal relationship between 6 gut microbial taxa and iNPH. We observed an inverse association between the Eubacterium fissicatena group (P = 0.007) and Lactococcus (P = 0.038) and iNPH, whereas Adlercreutzia (P = 0.029), Dialister (P = 0.040), Romboutsia (P = 0.027), Sutterella (P = 0.019) may be associated with an increased risk of iNPH. The results of the sensitivity analysis were robust.

Our findings suggest that certain gut bacteria may enhance iNPH risk. Research is required to determine whether the societal impact of iNPH is lessened in older people by sensible control of their gut microbiota.