Objective: We sought to determine whether fecal bile acids (BAs) could affect levodopa response assessed by levodopa challenge test (LCT) in patients with Parkinson’s disease (PD).

Background: Levodopa is the mainstay of treatments for PD, but large heterogeneity exists in patient response. Increasing evidence implicates bile acids (BAs) involved in the pathogenesis of PD. Furthermore, BAs have also participated in drug bioavailability. However, the impact of BAs on levodopa response (LR) has not been investigated.

Method: Levodopa challenge test (LCT) was conducted in 92 PD patients to assess LR. 36 fecal BAs and plasma levodopa concentrations were detected using LC-MS/MS. The difference of BAs between subgroups with bottom and top 30% LR were analyzed and fecal samples from the two groups were collected for metagenomic shotgun analysis.

Results: No fecal BAs were significantly correlated with LR, except for chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3-β-glucuronide, R = -0.228, P = 0.039). We found no significant difference of BAs between subgroups with bottom and top 30% LR (Fig.1). What is more, no significant changes in bacterial species composition related to bile acids metabolism or in the proportional representation of genes encoding known bile acids enzymes were observed between the groups (Fig.2).

Conclusion: Overall, our data do not support association of fecal BAs and levodopa response in PD patients. More precise macro-metablomic approach are needed in revealing the potential association between gut microbial interactions and treatment effect of levodopa.

Fig 1. Relationship between fecal BAs and LR.

Fig 2: Metagenomic sequencing data.

References: [1] Spanogiannopoulos P, Bess EN, Carmody RN, et al. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol 2016;14:273-287.
[2] Zhao Q, Chen Y, Huang W, et al. Drug-microbiota interactions: an emerging priority for precision medicine. Signal Transduct Target Ther 2023;8:386.
[3] Zhang Y, He X, Mo C, et al. Association Between Microbial Tyrosine Decarboxylase Gene and Levodopa Responsiveness in Patients With Parkinson Disease. Neurology 2022;99:e2443-e2453.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-fecal-bile-acids-and-levodopa-response-in-patients-with-parkinsons-disease/