Gut microbiome variation is associated to Multiple Sclerosis phenotypic subtypes

Reynders, Tatjana; Devolder, Lindsay; Valles‐Colomer, Mireia; Remoortel, Ann Van; Joossens, Marie; Keyser, Jacques De; Nagels, Guy; D’hooghe, Marie B.; Raes, Jeroen

doi:10.1002/acn3.51004

Cited by 76 publications

(69 citation statements)

References 52 publications

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“…MS is a multifaceted disease, comprising a range of disease subtypes [ 30 , 31 ], and with a variety of confounding factors involved in susceptibility, risk stratification, and treatment response capacities [ 32 , 33 ]. MS-centered studies therefore require strictly defined inclusion criteria, properly matched controls, and relatively large patient cohorts for clinical intervention studies.…”

Section: Discussionmentioning

confidence: 99%

The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

Yordanova

Ebner

Schulz

et al. 2021

Life

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Considering their potent immunomodulatory properties, therapeutic applications of Trichuris suis ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical phase 1 and 2 studies have demonstrated TSO treatment to be safe and well tolerated in MS patients, however, they reported only modest clinical efficacy. We therefore addressed the cellular and humoral immune responses directed against parasite antigens in individual MS patients receiving controlled TSO treatment (2500 TSO p.o. every 2 weeks for 12 month). Peripheral blood mononuclear cells (PBMC) of MS patients treated with TSO (n = 5) or placebo (n = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for T. suis excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DRhigh plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4+ and CD8+ T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR+CD4+ T cells in TSO-treated patients only. Frequencies of Gata3+ Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3+ Treg frequencies varied greatly between individuals. Using a T. suis antigen-specific T cell expansion assay, we also detected patient-to-patient variation of antigen-specific T cell recall responses and cytokine production. In summary, MS patients receiving TSO treatment established a T. suis-specific T- and B-cell response, however, with varying degrees of T cell responses and cellular functionality across individuals, which might account for the overall miscellaneous clinical efficacy in the studied patients.

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Section: Discussionmentioning

confidence: 99%

The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

Yordanova

Ebner

Schulz

et al. 2021

Life

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“…In seven studies, there were no specific descriptions of HC recruitment [39][40][41][42][43][44][45]. In three studies, HC were recruited from databases (Metabolic Department University Hospital Brussels [46], Norwegian Bone Marrow Donor Registry [37], Brigham and Women's Hospital PhenoGenetic project [47]). In four studies, HC were recruited from hospital staff or students (Hospital Brussels (para)medical staff [46], University of Manitoba Health Sciences Centre [36], Turkish hospital employees [38], Azabu University [48]).…”

Section: Description Of Included Studiesmentioning

confidence: 99%

“…In three studies, HC were recruited from databases (Metabolic Department University Hospital Brussels [46], Norwegian Bone Marrow Donor Registry [37], Brigham and Women's Hospital PhenoGenetic project [47]). In four studies, HC were recruited from hospital staff or students (Hospital Brussels (para)medical staff [46], University of Manitoba Health Sciences Centre [36], Turkish hospital employees [38], Azabu University [48]). In one study, family members were recruited [49] and in one study, the participants' proxies were included as HC [46].…”

Section: Description Of Included Studiesmentioning

confidence: 99%

“…In four studies, HC were recruited from hospital staff or students (Hospital Brussels (para)medical staff [46], University of Manitoba Health Sciences Centre [36], Turkish hospital employees [38], Azabu University [48]). In one study, family members were recruited [49] and in one study, the participants' proxies were included as HC [46]. In four studies, HC and patients are matched for age [39,42,46,47].…”

Section: Description Of Included Studiesmentioning

confidence: 99%

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Faecal Microbiota in Patients with Neurogenic Bowel Dysfunction and Spinal Cord Injury or Multiple Sclerosis—A Systematic Review

Faber

Stolwijk-Swüste

Ginkel

et al. 2021

JCM

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Background: Neurogenic bowel dysfunction (NBD) frequently occurs in patients with spinal cord injury (SCI) and multiple sclerosis (MS) with comparable symptoms and is often difficult to treat. It has been suggested the gut microbiota might influence the course of NBD. We systematically reviewed the literature on the composition of the gut microbiota in SCI and MS, and the possible role of neurogenic bowel function, diet and antibiotic use. Methods: A systematic search was conducted in PubMed and Embase, which retrieved studies on the gut microbiota in SCI and MS. The Newcastle–Ottawa Quality Assessment Scale (NOS) was used to assess methodological quality. Results: We retrieved fourteen papers (four on SCI, ten on MS), describing the results of a total of 479 patients. The number of patients per study varied from 13 to 89 with an average of 34. Thirteen papers were observational studies and one study was an intervention study. The studies were case control studies in which the gut microbiota composition was determined by 16S rRNA gene sequencing. The methodological quality of the studies was mostly rated to be moderate. Results of two studies suggested that alpha diversity in chronic SCI patients is lower compared to healthy controls (HC), whereas results from five studies suggest that the alpha diversity of MS patients is similar compared to healthy subjects. The taxonomic changes in MS and SCI studies are diverse. Most studies did not account for possible confounding by diet, antibiotic use and bowel function. Conclusion: Based on these 14 papers, we cannot draw strong conclusions on the composition of the gut microbiota in SCI and MS patients. Putatively, alpha diversity in chronic SCI patients may be lower compared to healthy controls, while in MS patients, alpha diversity may be similar or lower compared to healthy controls. Future studies should provide a more detailed description of clinical characteristics of participants and of diet, antibiotic use and bowel function in order to make valid inferences on changes in gut microbiota and the possible role of diet, antibiotic use and bowel function in those changes.

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“…Additionally, a disruption in sIgA production could drive to an impairment in the gut immune function with further consequences for several inflammatory diseases, such as e.g., the MS (Okai et al, 2016;Salas-Cuestas et al, 2017;Morshedi et al, 2019;Mirza et al, 2020;Reynders et al, 2020). There is a close relationship between IgA and colitogenic bacteria that increase the risk for intestinal diseases, as evidence shows that this immunoglobulin coats several of these bacteria (Palm et al, 2014;Rojas et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

No Impact of Long-Term Fingolimod Treatment on Fecal Secretory Immunoglobulin A Levels in Patients With Multiple Sclerosis

Inojosa

Eisele

Proschmann

et al. 2020

Front. Cell Dev. Biol.

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Background: Fingolimod (FTY) is a sphingosine 1 phosphate (S1P) agonist with significant effects on immune cell distribution used as an effective disease modifying therapy in multiple sclerosis (MS) patients. Animal studies have demonstrated that a dysregulation of egress of murine secretory Immunglobulin A (sIgA)+ plasmablasts from Peyer's patches in FTY-treated mice reduced fecal sIgA levels. Alterations in intestinal levels of sIgA could modify the gut microbiome and homeostasis in humans. We analyzed the effect of FTY on the fecal and salivary sIgA levels as marker of the humoral immune system in the gut. Methods: Twenty five people with confirmed MS diagnosis according to 2010 revised McDonald's criteria and on long-term continuous treatment at the MS Center in Dresden, Germany were enrolled in this exploratory cross-sectional study. Fecal and salivary sIgA were analyzed after at least 12 months of treatment with FTY or Glatiramer acetate (GA). Results: Fifteen MS patients on FTY and 10 on GA participated in this study. The mean fecal sIgA concentration of both groups was not decreased compared to reference values and did not demonstrate significant differences between them (FTY 3323.13 µg/g +/− 2094.72; GA 2040.65 µg/g +/− 1709.07). A similar pattern was seen in the salivary sIgA and serum immunoglobulins levels. Conclusion: In this pilot study, we could not confirm the decrease of fecal sIgA after a long-term treatment with FTY. Further longitudinal studies should evaluate the effects of MS treatments on the gut immune system in more detail.

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Gut microbiome variation is associated to Multiple Sclerosis phenotypic subtypes

Cited by 76 publications

References 52 publications

The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

Faecal Microbiota in Patients with Neurogenic Bowel Dysfunction and Spinal Cord Injury or Multiple Sclerosis—A Systematic Review

No Impact of Long-Term Fingolimod Treatment on Fecal Secretory Immunoglobulin A Levels in Patients With Multiple Sclerosis

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