B-cell-depletion reverses dysbiosis of the microbiome in multiple sclerosis patients

Alba Troci,Olga Zimmermann,Klarissa Hanja Stürner,Frank Leypoldt,Andre Franke,Corinna Bang,Sandra May,Paula Krampitz,Daniela Berg,Daniela Esser

doi:10.1038/s41598-022-07336-8

Abstract

To elucidate cross-sectional patterns and longitudinal changes of oral and stool microbiota in multiple sclerosis (MS) patients and the effect of B-cell depletion. We conducted an observational, longitudinal clinical cohort study analysing four timepoints over 12 months in 36 MS patients, of whom 22 initiated B-cell depleting therapy with ocrelizumab and a healthy control group. For microbiota analysis of the oral cavity and the gut, provided stool and oral swab samples underwent 16S rDNA sequencing and subsequent bioinformatic analyses. Oral microbiota-patterns exhibited a reduced alpha-diversity and unique differential microbiota changes compared to stool such as increased levels of Proteobacteria and decreased abundance of Actinobacteria. Following B-cell depletion, we observed increased alpha-diversity in the gut and the oral cavity as well as a long-term sustained reduction of pro-inflammatory Gram-negative bacteria (e.g., Escherichia/Shigella). MS patients have altered stool and oral microbiota diversity patterns compared to healthy controls, which are most pronounced in patients with higher disease activity and disability. Therapeutic B-cell depletion is associated with persisting regression of these changes. Whether these microbial changes are unspecific side-effects of B-cell depletion or indirectly modulate MS disease activity and progression is currently unknown and necessitates further investigations.

Highlights

To elucidate cross-sectional patterns and longitudinal changes of oral and stool microbiota in multiple sclerosis (MS) patients and the effect of B-cell depletion
We found a significant decrease of members of the genera Haemophilus and Lautropia out of the Proteobacteria, Porphyromonas out of the Bacteroidetes, Veillonella and Granulicatella out of the Firmicutes as well as unclassified members from the phylum Candidatus Saccharibacteria
Key findings of our study are (I) the specific microbial fingerprint observed in oral swabs in MS patients, (II) the stool microbial changes associated with disease severity at baseline and (III) the persisting long-term reversibility of these compositional differences following B-cell depletion

Summary

Introduction

To elucidate cross-sectional patterns and longitudinal changes of oral and stool microbiota in multiple sclerosis (MS) patients and the effect of B-cell depletion. There is increasing evidence that an altered microbiome composition might influence the progression of MS— data on longitudinal persistence of microbial changes, differences between the oral and aboral microbiota and the effect of immunotherapy on microbial composition is still lacking. This lack of data on oral microbiota is remarkable since impaired oral health of MS patients has already been described 30 years ago[5] and there is increasing evidence that bacteria of the oral cavity can directly influence neuro-immune activity and inflammation[6,7]. Due to the high efficacy in controlling inflammation in MS by the monoclonal B-cell-depleting antibody ocrelizumab (Ocrevus®) for relapsing–remitting MS, we initiated a longitudinal, observational study recruiting patients with planned B-cell depletion therapy and age- and gender-matched patients who decided against immunotherapy

Methods

Results

Discussion

Conclusion