Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease

Mangalam, Ashutosh K.; Shahi, Shailesh K.; Luckey, David; Karau, Melissa J.; Marietta, Eric; Luo, Ningling; Choung, Rok Seon; Ju, Josephine M.; Sompallae, Ramakrishna; Gibson‐Corley, Katherine N.; Patel, Robin; Rodriguez, Moses; David, Chella S.; Taneja, Veena; Murray, Joseph A.

doi:10.1016/j.celrep.2017.07.031

Cited by 240 publications

(215 citation statements)

References 29 publications

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“…Tryptophan‐derived aryl hydrocarbon receptor ligands produced by intestinal commensals can reach the central nervous system (CNS) to modulate astrocyte function and suppress inflammation and neurodegeneration . A recent study showed that the human gut‐derived commensal Prevotella suppresses EAE in a human leukocyte antigen (HLA) class II transgenic mouse model …”

supporting

confidence: 53%

“…9 A recent study showed that the human gut-derived commensal Prevotella suppresses EAE in a human leukocyte antigen (HLA) class II transgenic mouse model. 10 Alterations in the gut microbiome of MS patients has been reported by a number of investigators. We have found increased Methanobrevibacter and decreased Butyricimonas in the gut microbiome of MS patients.…”

mentioning

confidence: 96%

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A probiotic modulates the microbiome and immunity in multiple sclerosis

Tankou

Regev

Healy

et al. 2018

Annals of Neurology

194

116

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Objective Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. Methods MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. Results Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients such as methane metabolism following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased HLA-DR MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic induced increased in the abundance of Lactobacillus and Bifidobacterium were associated with decreased expression of MS risk allele HLA.DPB1 in controls. Interpretation Our results suggest that probiotic could have a synergistic effect with current MS therapies.

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supporting

confidence: 53%

mentioning

confidence: 96%

A probiotic modulates the microbiome and immunity in multiple sclerosis

Tankou

Regev

Healy

et al. 2018

Annals of Neurology

194

116

View full text Add to dashboard Cite

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“…Further analysis of commensal bacteria at the family and genus level revealed only minor differences between BACHD and WT mice, where both 3 and 6 month old BACHD mice showed decreased abundance of Prevotella and Bacteroides at the genera level, part of the phylum Bacteroidetes. Consistent with our findings, Prevotella was previously reported to be decreased in the APP/PS1 transgenic mouse model of AD (Shen et al, 2017) and in the experimental autoimmune encephalomyelitis mouse, which recapitulates the main characteristic of MS (Mangalam et al, 2017). Moreover, microbiota profiling in humans also showed decreased Prevotella abundance in MS patients (Chen et al, 2016;Jangi et al, 2016), autistic children (Kang et al, 2013), and PD patients (Keshavarzian et al, 2015;Scheperjans et al, 2015), and was associated with increased gut permeability (Hasegawa et al, 2015).…”

Section: Characterisation Of Microbiota In Bachd and Wt Mice Housed Usupporting

confidence: 90%

Manipulation of microbiota reveals altered myelination and white matter plasticity in a model of Huntington disease

Radulescu

Garcia-Miralles

Sidik

et al. 2018

Preprint

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Structural and molecular myelination deficits represent early pathological features ofHuntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD.Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions.Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.

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“…14 A recent study showed that the human gut-derived commensal Prevotella suppresses EAE in a human leukocyte antigen (HLA) class II transgenic mouse model. 15 We have reported alteration in the gut microbiome of MS patients. 6 Several other groups have also reported dysbiosis in the gut microbiome of MS subjects.…”

Section: Introductionmentioning

confidence: 95%

Investigation of probiotics in multiple sclerosis

et al. 2018

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None of the disease-modifying therapies (DMTs) currently being used for the management of multiple sclerosis (MS) are 100% effective. In addition, side effects associated with the use of these DMTs have limited the practice of combination therapy. Hence, there is a need for safe immunomodulatory agents to fine-tune the management of MS. The gut microbiome plays an important role in autoimmunity, and several studies have reported alterations in the gut microbiome of MS patients. Studies in animal model of MS have identified members of the gut commensal microflora that exacerbate or ameliorate neuroinflammation. Probiotics represent an oral, non-toxic immunomodulatory agent that could be used in combination with current MS therapy. We designed a pilot study to investigate the effect of VSL3 on the gut microbiome and peripheral immune system function in healthy controls and MS patients. VSL3 administration was associated with increased abundance of many taxa with enriched taxa predominated by Lactobacillus, Streptococcus, and Bifidobacterium species. At the immune level, VSL3 administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of intermediate monocytes (CD14CD16), decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased human leukocyte antigen-antigen D related (HLA-DR) MFI on dendritic cells.

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Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease

Cited by 240 publications

References 29 publications

A probiotic modulates the microbiome and immunity in multiple sclerosis

A probiotic modulates the microbiome and immunity in multiple sclerosis

Manipulation of microbiota reveals altered myelination and white matter plasticity in a model of Huntington disease

Investigation of probiotics in multiple sclerosis

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