Gut microbiota in early pediatric multiple sclerosis: a case−control study

Abstract

Background Alterations in the gut microbial community composition maybe influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex. Methods Children ≤18 years old within two years of MS onset, or controls without autoimmune disorders attending a University of California, San Francisco, USA pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and Phylogenetic Reconstruction of Unobserved States (PICRUST) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression. Results Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range 4-18) were studied. Cases had a short disease duration (mean=11 months; range 2-24) and half were immunomodulatory (IMD) drug naïve. While overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, p<0.02). However relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all p and q<0.000005). Microbial genes predicted as enriched in MS vs. controls included those involved in glutathione metabolism (Mann-Whitney, p=0.017); findings that were consistent regardless of IMD exposure. Conclusions In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu.

Breaking down the gut microbiome composition in multiple sclerosis

“…27,38 Interestingly, Jangi et al 7 found increased Methanobrevibacter among 60 RRMS patients compared to controls. Tremlett et al 6 similarly found enrichment of Methanobrevibacter among their patients with pediatric early MS. Castillo Alvarez et al, 8 however, found a lower abundance of Archaea among 30 MS patients compared to controls, suggesting that further investigation of the relationship between Methanobrevibacter and MS is warranted. Importantly, the association between constipation and increased methanogenic archaea is a potential confounder that should be controlled for in future studies, given the high prevalence of constipation in MS. 7,26 Other microorganisms Several other differences in the gut microbiome of MS patients have been identified.…”

“…Instead, enrichment or depletion of a limited number of taxa seems to be a reproducible finding. 6,7 We systematically review alterations in the gut microbiota that have been identified in patients with MS (see Table 1) and discuss their potential contributions to MS pathogenesis (see Table 2). …”

Gut Microbiome in Inflammatory Bowel Disease and Other Chronic Immune-Mediated Inflammatory Diseases

“…Tremlett et al [30] studied the gut microbiota in pediatric patients with relapsing/remitting MS and found that relative to controls, MS cases had a significant enrichment in the relative abundance for members of the Desulfovibrionaceae family and depletion in Lachnospiraceae and Ruminococcaceae (all p < 0.000005). They further showed that microbiota richness correlated positively with Th17 for cases but not controls, whereas Bacteroidetes inversely correlated with Th17 for cases but not controls.…”

The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis

“…Many of the studies shown in Table 1 have been recently reviewed by Newland et al (19). The studies conducted so far suggest the presence of a disrupted or altered microbiota in MS patients when compared to healthy controls (12)(13)(14)(15)(16)(17)(18). All studies were performed in patients diagnosed with relapsing remitting MS, and in some the effects of immunomodulatory therapies were evaluated (13,18).…”