There have been a few papers in the microbiome world recently for you to digest.

Tremmlet et al. The gut microbiota in pediatric multiple sclerosis and demyelinating syndromesAnn Clin Transl Neurol 2021 Dec 9. doi: 10.1002/acn3.51476. 

Objective: To examine the gut microbiota in individuals with and without pediatric-onset multiple sclerosis (MS).

Methods: We compared stool-derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease-modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset <18 years), and unaffected controls. All were ≥30 days without antibiotics or corticosteroids. V4 region 16S RNA gene-derived amplicon sequence variants (Illumina MiSeq) were assessed using negative binomial regression and network analyses; rate ratios were age- and sex-adjusted (aRR).

Results: Thirty-two MS, 41 monoADS (symptom onset [mean] = 14.0 and 6.9 years) and 36 control participants were included; 75%/56%/58% were female, with mean ages at stool sample = 16.5/13.8/15.1 years, respectively. Nine MS cases (28%) were DMD-naïve. Although microbiota diversity (alpha, beta) did not differ between participants (p > 0.1), taxa-level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6-11.2, p = 0.004, Q = 0.01), and lower abundances of short-chain fatty acid (SCFA)-producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q < 0.05). DMD-naïve MS cases were depleted for Clostridiales vadin-BB60 (unnamed species) versus either DMD-exposed, controls (p, Q < 0.01), or monoADS (p = 0.001, Q = 0.06) and exhibited altered community connectedness (p < 10-9 Kruskal-Wallis), with SCFA-producing taxa underrepresented. Consistent taxa-level findings from an independent US Network of Pediatric MS Centers case/control (n = 51/42) cohort included >eightfold higher abundance for Candidatus Stoquefichus and Tyzzerella (aRR = 8.8-12.8, p < 0.05) in MS cases and 72%-80% lower abundance of SCFA-producing Ruminococcaceae-NK4A214 (aRR = 0.38-0.2, p ≤ 0.01).

Interpretation: Gut microbiota community structure, function and connectivity, and not just individual taxa, are of likely importance in MS.

This is a study of microbiome in children for those interested you can have a read. I guess one problem of these observational studies is you ask is this the “chicken or the egg” what comes first, what changes in the microbiome are important? Is it microbiome then MS or MS and then the microbiome. This has been discussed recently if you are interested

Parodi B, Kerlero de Rosbo N. The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease? Front Immunol. 2021 Sep 21;12:718220.

I guess we have to wait and see what replicates and what does not.

I guess this in part depends on where you do the studies

Cox LM, Maghzi AH, Liu S, Tankou SK, Dhang FH, Willocq V, Song A, Wasén C, Tauhid S, Chu R, Anderson MC, De Jager PL, Polgar-Turcsanyi M, Healy BC, Glanz BI, Bakshi R, Chitnis T, Weiner HL. Gut Microbiome in Progressive Multiple Sclerosis. Ann Neurol. 2021;89(6):1195-1211.

Objective: This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease.

Methods: We sequenced the microbiota from healthy controls and relapsing-remitting MS (RRMS) and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including Expanded Disability Status Scale (EDSS), quality of life, and brain magnetic resonance imaging lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis (EAE).

Results: Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17-producing γδ T cells.

Interpretation: Whereas some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome

Elgendy SG, Abd-Elhameed R, Daef E, Mohammed SM, Hassan HM, El-Mokhtar MA, Nasreldein A, Khedr EM. Gut microbiota in forty cases of egyptian relapsing remitting multiple sclerosis. Iran J Microbiol. 2021 Oct;13(5):632-641.

Background: Microorganisms in oral cavity are called oral microbiota, while microbiome consists of total genome content of microorganisms in a host. Interaction between host and microorganisms is important in nervous system development and nervous diseases such as Autism, Alzheimer, Parkinson and Multiple Sclerosis (MS). Bacterial infections, as an environmental factor in MS pathogenesis play role in T helper 17(Th17) increase and it enhancing the production of pro-inflammatory cytokines such as Interlukin-21(IL-21), IL-17 and IL -22. Oral microbiota consists diverse populations of cultivable and uncultivable bacterial species. Denaturing gradient gel electrophoresis (DGGE) is an acceptable method for identification of uncultivable bacteria. In this study, we compared the bacterial population diversity in the oral cavity between MS and healthy people.

Methods: From October to March 2019, samples were taken at Kermanshah University of Medical Sciences’ MS patients center. A total of 30 samples were taken from MS patients and another 30 samples were taken from healthy people. Phenotypic tests were used to identify bacteria after pure cultures were obtained. DNA was extracted from 1 mL of saliva, and PCR products produced with primers were electrophoresed on polyacrylamide gels.

Results: The genera Staphylococcus, Actinomyces, Fusobacterium, Bacteroides, Porphyromonas, Prevotella, Veillonella, Propionibacterium and uncultivable bacteria with accession number MW880919-25, JQ477416.1, KF074888.1 and several other un-culturable strains were significantly more abundant in the MS group while Lactobacillus and Peptostreptococcus were more prevalent in the normal healthy group according to logistic regression method.

Conclusion: Oral micro-organisms may alleviate or exacerbate inflammatory condition which impact MS disease pathogenesis. It may be assumed that controlling oral infections may result in reduction of MS disease progression.

Elgendy SG, Abd-Elhameed R, Daef E, Mohammed SM, Hassan HM, El-Mokhtar MA, Nasreldein A, Khedr EM. Gut microbiota in forty cases of egyptian relapsing remitting multiple sclerosis. Iran J Microbiol. 2021 Oct;13(5):632-641.

Background and objectives: Gut microbiota is assumed to play an essential role in the pathogenesis of multiple sclerosis (MS). This study aimed to investigate the abundance of some gut microbiota among Egyptian patients with relapsing remitting multiple sclerosis (RR-MS).

Materials and methods: Forty cases of RR-MS diagnosed according to McDonald diagnostic criteria (2017) were recruited consecutively from the Department of Neurology, Assiut University Hospitals. The results were compared with 22 healthy age and sex matched control subjects. DNA was extracted from stool and measures made of concentration and copy number of bacterial organisms by real-time PCR using group specific primers for 16S rRNA targeting predominant genera of gut microbiota previously hypothesized to participate in MS pathogenesis.

Results: The mean age was 31.4 ± 8.8 yrs; 75% of the patients were women. The mean and SD of EDSS score was 3.43 ± 1.35. Seven cases had cervical cord plaques (17%). There were significantly increased copy numbers of Desulfovibrio, Actinobacteria, Firmcutes, and Lactic acid bacteria in patients compared with the control group. In contrast there was a significantly lower level of Clostridium cluster IV in the patients. Patients who had EDSS < 3.5 had a significantly higher copy number of Actinobacteria, Bacteroidetes, and Bifidobacterium, compared with patients who had EDSS > 3.5. There was a significant negative correlation between duration of illness and copy number of Firmcutes, Akkermansia, and Lactic acid bacteria (P = 0.01, 0.04, and 0.004 respectively).

Conclusion: The changes in gut microbiota are associated with exacerbation of MS disease. Disruption of the intestinal microbiota results in the depletion or enrichment of certain bacteria that may affect the immune balance leading to predisposition to MS.

Are you interested in ths stuff?

Is a repeated long list of gut flora? Maybe someone can make it interesting for you.

Clostridea bacteria made me prick up my ears as I could make a potential nice link to autoimmune problems and alemtuzumab, But what do you find in alemtuzumab-treated individuals? During lock-down our freezers have become filled up with all sorts of SH1…but with microbiome stuff they really have:-)

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