Mycobacterium avium subspecies paratuberculosis (MAP) infection, and its impact on gut microbiome of individuals with Multiple Sclerosis

Abstract

Background There is a growing body of evidence suggesting the role of gut microbiome in the aetiology of Multiple sclerosis (MS) with the development and progression of the disease as a multifactorial interaction between the gut, the brain, and the immune system. At the same time there is also existing evidence to link Mycobacterium avium subspecies paratuberculosis infections (MAP) and the development of MS. Whilst perturbations of the gut microbiome in patients with MS are well described in the literature, nothing is known about the gut microbiome perturbations in MAP infected MS patients. In the present study, using 16S rRNA amplification, we characterize the compositional and functional differences of the gut microbiome between MS patients with MAP (MAP+) and without (MAP-) infection and compare the results with a healthy cohort to understand the gut microbiome dynamics. Results Based on diversity analyses, there were notable differences between HC, MAP-, and MAP + profiles. Fitting neutral modelling on core microbiome, we have found taxa selected by the hosts, and those that were based on dispersal limitation. Core phyla shared between MAP + and MAP- belonged to Actinobacteria, Bacteroidata, Verrucomicrobiota, Firmicutes, with additional Desulfobacterota, and Proteobacteria observed in MAP + only. Using a Quasi Conditional Association Test, Archaea were over represented in MS samples, particularly in MAP+. Using contingency analyses, we are able to identify discriminatory patterns between MAP statuses in the context of anthropometric and sociodemographic patterns. Finally, an advanced mediation analysis then consolidates confounders, treatment groups, microbiome, and the outcome parameters (including disease duration). This highlighted certain species i.e., Sutterella, Akkermmansia, Bacteriodes, Gastranaerophilales, Alistipes, Balutia, Faecalibacterium, Lachnospiraceae, Anaerostipes, Ruminococcaceae, Eggerthellaceae and Clostridia-UCG-014 having mediatory effect considering disease duration as an outcome and MAP as a treatment group. Conclusions Overall, we found that there were profound differences in the composition and function of the gut microbiome between MAP + and MAP- MS patients, with the difference in taxonomic structure being greater than the functional difference. Our analysis indicates that the gut microbiome may be an important target for dietary and lifestyle intervention in MS patients with and without MAP infection.

Integrative multi-cohort analysis reveals consistent sex differences in gut microbiota of multiple sclerosis patients

“…The increased permeability of the gastrointestinal and blood-brain barriers associated with MS may facilitate the translocation of bacterial components that can influence the synthesis and maintenance of the myelin sheath (9, 10). In human cohorts, multiple investigations have reported alterations in the abundance of specific taxa when comparing gut microbiomes of patients with MS to healthy controls (6, 11–21). However, these findings have not been consistent across studies (22, 23), prompting efforts to integrate results across cohorts (24, 25).…”

Integrative multi-cohort analysis reveals consistent sex differences in gut microbiota of multiple sclerosis patients

“…The increased permeability of the gastrointestinal and blood-brain barriers associated with MS may facilitate the translocation of bacterial components that can influence the synthesis and maintenance of the myelin sheath (9, 10). In human cohorts, multiple investigations have reported alterations in the abundance of specific taxa when comparing gut microbiomes of patients with MS to healthy controls (6, 11–21). However, these findings have not been consistent across studies (22, 23), prompting efforts to integrate results across cohorts (24, 25).…”

Integrative multi-cohort analysis reveals consistent sex differences in gut microbiota of multiple sclerosis patients

“…The increased permeability of the gastrointestinal and blood-brain barriers associated with MS may facilitate the translocation of bacterial components that can influence the synthesis and maintenance of the myelin sheath (9, 10). In human cohorts, multiple investigations have reported alterations in the abundance of specific taxa when comparing gut microbiomes of patients with MS to healthy controls (6, 11–21). However, these findings have not been consistent across studies (22, 23), prompting efforts to integrate results across cohorts (24, 25).…”

Integrative multi-cohort analysis reveals consistent sex differences in gut microbiota of multiple sclerosis patients

“…The increased permeability of the gastrointestinal and blood-brain barriers associated with MS may facilitate the translocation of bacterial components that can influence the synthesis and maintenance of the myelin sheath (9, 10). In human cohorts, multiple investigations have reported alterations in the abundance of specific taxa when comparing gut microbiomes of patients with MS to healthy controls (6, 11–21). However, these findings have not been consistent across studies (22, 23), prompting efforts to integrate results across cohorts (24, 25).…”