Gut microbiota composition and relapse risk in pediatric MS: A pilot study

Tremlett, Helen; Fadrosh, Douglas; Faruqi, Ali A.; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Lynch, Susan V.; Waubant, Emmanuelle; Aaen, Greg; Belman, Anita; Benson, Leslie; Casper, Charlie; Chitnis, Tanuja; Gorman, Mark; Harris, Yolanda; Krupp, Lauren; Lotze, Tim; Lulu, Sabina; Ness, Jayne; Olsen, Cody S.; Roan, Erik; Rodriguez, Moses; Rose, John; Simmons, Timothy; Tillema, Jan Mendelt; Weber, Wendy; Weinstock‐Guttman, Bianca

doi:10.1016/j.jns.2016.02.042

Cited by 145 publications

(126 citation statements)

References 14 publications

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“…Similar modest differences, are reported in other autoimmune disease and are suggestive of ongoing inflammation (12,13). Further, gut microbiota composition has also been associated with relapse risk in paediatric MS (11). Larger, longitudinal studies are needed to better understand potential confounders, from comorbidity to concomitant medications.…”

supporting

confidence: 55%

The multiple sclerosis microbiome?

Tremlett¹,

Waubant²

2017

Ann. Transl. Med.

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supporting

confidence: 55%

The multiple sclerosis microbiome?

Tremlett¹,

Waubant²

2017

Ann. Transl. Med.

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“…Stool samples were available from 17 of the 82 cases in the discovery set 28. We extracted and amplified DNA from stool samples and performed 16S rRNA sequencing.…”

Section: Methodsmentioning

confidence: 99%

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Nourbakhsh

Bhargava

Tremlett

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children.MethodsParticipants with pediatric‐onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox‐proportional hazard models were used.ResultsUsing global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota‐derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota‐derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4–34%) and 32% (95% CI: 16–44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk.InterpretationTrp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.

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“…However, using the relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis, it has been shown that the commensal gut flora -in the absence of pathogenic agents -is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4 + T cells. 81,82 Further research is now ongoing to determine the composition of the intestinal microbiota associated with an increased susceptibility to MS, 83,84 in addition to disease outcomes in those already with MS, 85 and this research may provide a conceptual basis for exploring new, less invasive treatment strategies.…”

Section: Implications For Patient Carementioning

confidence: 99%

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

et al. 2017

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Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS), most likely autoimmune in origin, usually beginning in early adulthood. The aetiology of the disease is not well understood; it is viewed currently as a multifactorial disease which results from complex interactions between genetic predisposition and environmental factors, of which a few are potentially modifiable. Improving our understanding of these factors can lead to new and more effective approaches to patient counselling and, possibly, prevention and management of the disease. The 2016 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) addressed the topic of environmental, modifiable risk factors for MS, gathering experts from around the world, to collate experimental and clinical research into environmental factors that have been associated with the disease onset and, in a few cases, disease activity and progression. A number of factors, including infections, vitamin D deficiency, diet and lifestyle factors, stress and comorbidities, were discussed. The meeting provided a forum to analyse available evidence, to identify inconsistencies and gaps in current knowledge and to suggest avenues for future research.

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Gut microbiota composition and relapse risk in pediatric MS: A pilot study

Cited by 145 publications

References 14 publications

The multiple sclerosis microbiome?

The multiple sclerosis microbiome?

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

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