PMID- 29679417 OWN - NLM STAT- MEDLINE DCOM- 20190812 LR - 20230928 IS - 1531-8249 (Electronic) IS - 0364-5134 (Print) IS - 0364-5134 (Linking) VI - 83 IP - 6 DP - 2018 Jun TI - A probiotic modulates the microbiome and immunity in multiple sclerosis. PG - 1147-1161 LID - 10.1002/ana.25244 [doi] AB - OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (MS) 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 Encyclopedia 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 human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic-induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls. INTERPRETATION: Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018. CI - (c) 2018 American Neurological Association. FAU - Tankou, Stephanie K AU - Tankou SK AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Regev, Keren AU - Regev K AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Healy, Brian C AU - Healy BC AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Tjon, Emily AU - Tjon E AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Laghi, Luca AU - Laghi L AD - University of Bologna, Department of Agricultural and Food Sciences, Cesena 47521, Italy. FAU - Cox, Laura M AU - Cox LM AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Kivisakk, Pia AU - Kivisakk P AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Pierre, Isabelle V AU - Pierre IV AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Hrishikesh, Lokhande AU - Hrishikesh L AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Gandhi, Roopali AU - Gandhi R AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. FAU - Cook, Sandra AU - Cook S AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Glanz, Bonnie AU - Glanz B AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Stankiewicz, James AU - Stankiewicz J AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Weiner, Howard L AU - Weiner HL AD - Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. AD - Evergrande Center for Immunologic Diseases. LA - eng GR - R01 NS087226/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180608 PL - United States TA - Ann Neurol JT - Annals of neurology JID - 7707449 RN - 0 (RNA, Ribosomal, 16S) MH - Adult MH - Bifidobacterium/genetics/*immunology MH - Female MH - Gastrointestinal Microbiome/physiology MH - Humans MH - Lactobacillus/genetics/immunology MH - Leukocytes, Mononuclear/metabolism MH - Male MH - Microbiota/genetics/*immunology MH - Middle Aged MH - Multiple Sclerosis/*genetics/immunology MH - Probiotics/*metabolism MH - RNA, Ribosomal, 16S/genetics MH - Young Adult PMC - PMC6181139 MID - NIHMS975663 COIS- Potential Conflicts of Interest: This study was supported in part by Teva Neuroscience (Teva manufactures the drug glatiramer acetate used in this study). EDAT- 2018/04/22 06:00 MHDA- 2019/08/14 06:00 PMCR- 2018/10/11 CRDT- 2018/04/22 06:00 PHST- 2017/11/13 00:00 [received] PHST- 2018/04/16 00:00 [revised] PHST- 2018/04/18 00:00 [accepted] PHST- 2018/04/22 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2018/04/22 06:00 [entrez] PHST- 2018/10/11 00:00 [pmc-release] AID - 10.1002/ana.25244 [doi] PST - ppublish SO - Ann Neurol. 2018 Jun;83(6):1147-1161. doi: 10.1002/ana.25244. Epub 2018 Jun 8.