scholarly journals Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis

2021 ◽  
Vol 8 (4) ◽  
pp. e997
Author(s):  
Delphine Sterlin ◽  
Martin Larsen ◽  
Jehane Fadlallah ◽  
Christophe Parizot ◽  
Marina Vignes ◽  
...  

ObjectiveBased on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.MethodsWe investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.ResultsWe show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = −0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).ConclusionsGut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1938
Author(s):  
Han Aricha ◽  
Huasai Simujide ◽  
Chunjie Wang ◽  
Jian Zhang ◽  
Wenting Lv ◽  
...  

Mongolian cattle from China have strong adaptability and disease resistance. We aimed to compare the gut microbiota community structure and diversity in grazing Mongolian cattle from different regions in Inner Mongolia and to elucidate the influence of geographical factors on the intestinal microbial community structure. We used high throughput 16S rRNA sequencing to analyze the fecal microbial community and diversity in samples from 60 grazing Mongolian cattle from Hulunbuir Grassland, Xilingol Grassland, and Alxa Desert. A total of 2,720,545 high-quality reads and sequences that were 1,117,505,301 bp long were obtained. Alpha diversity among the three groups showed that the gut microbial diversity in Mongolian cattle in the grasslands was significantly higher than that in the desert. The dominant phyla were Firmicutes and Bacteroidetes, whereas Verrucomicrobia presented the highest abundance in the gut of cattle in the Alxa Desert. The gut bacterial communities in cattle from the grasslands versus the Alxa Desert were distinctive, and those from the grasslands were closely clustered. Community composition analysis revealed significant differences in species diversity and richness. Overall, the composition of the gut microbiota in Mongolian cattle is affected by geographical factors. Gut microbiota may play important roles in the geographical adaptations of Mongolian cattle.


2019 ◽  
Vol 28 (12) ◽  
pp. 1507-1527 ◽  
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Placido Bramanti ◽  
Emanuela Mazzon

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing–remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.


2019 ◽  
Vol 8 (10) ◽  
pp. 1605 ◽  
Author(s):  
Pełka-Wysiecka ◽  
Kaczmarczyk ◽  
Bąba-Kubiś ◽  
Liśkiewicz ◽  
Wroński ◽  
...  

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5–20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy; in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1024 ◽  
Author(s):  
Guillaume B. Fond ◽  
Jean-Christophe Lagier ◽  
Stéphane Honore ◽  
Christophe Lancon ◽  
Théo Korchia ◽  
...  

Background and significance. There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. Method. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. Results. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics’ impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Conclusion. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.


2020 ◽  
Vol 5 (53) ◽  
pp. eabc7191
Author(s):  
Anne-Katrin Pröbstel ◽  
Xiaoyuan Zhou ◽  
Ryan Baumann ◽  
Sven Wischnewski ◽  
Michael Kutza ◽  
...  

Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota–specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.


Author(s):  
Beata Zwiernik ◽  
Tomasz Arłukowicz ◽  
Marcin Mycko ◽  
Jacek Zwiernik

Introduction: Multiple sclerosis (MS) is caused by the abnormal activity of the immune system. It is believed that the pathological immune response may be initiated in the intestines, the area of the largest antigen presentation. This is where autoreactive T and B cells are activated, which constitutes the pathomechanism of this disease. In a healthy organism, normal gut microbiota mediates the balance between pro- and anti-inflammatory activity of the immune system. Aim: This paper aims at describing the healthy gut microbiota, its changes in MS patients, factors that influence its composition and therapeutic corrective possibilities. Material and methods: The paper is based on available medical literature. Results and discussion: It has been evidenced that in MS patients the gut microbiota is dominated by pro-inflammatory species. This may be caused by environmental factors, for instance, the diet, antibiotics or stimulants. Methods of the microbiota correction involve dietary change, prebiotics and probiotics as well as fecal microbiota transplantation (FMT). FMT is a particularly safe and promising method that has proven its efficiency on an animal model of MS. Conclusions: Experimental research has revealed that the correction of the gut microbiota may lead to MS remission or alleviation. FMT utilized in inflammatory bowel disease seems to be presently the most comprehensive intervention. Since only incidental reports of its efficiency in humans are presently available, further clinical studies are necessary.


2020 ◽  
Author(s):  
Jeremiah J. Faith ◽  
Alice Chen-Liaw ◽  
Varun Aggarwala ◽  
Nadeem O. Kaakoush ◽  
Thomas J. Borody ◽  
...  

SummaryThe population structure of strains within a bacterial species is poorly defined, despite the functional importance of strain variation in the human gut microbiota on health. Here we analyzed >1000 sequenced bacterial strains from the fecal microbiota of 47 individuals from two countries and combined them with >150,000 bacterial genomes from NCBI to quantify the strain population size of different bacterial species, as well as the frequency of finding the same strain colonized in unrelated individuals who had no opportunities for direct microbial strain transmission. Strain population sizes ranged from tens to over one-hundred thousand per species. Prevalent strains in common gut microbiota species with small population sizes were the most likely to be harbored in two or more unrelated individuals. The finite strain population size of certain species creates the opportunity to comprehensively sequence the entirety of these species’ prevalent strains and associate their presence in different individuals with health outcomes.


2021 ◽  
Vol 13 (1S) ◽  
pp. 27-30
Author(s):  
A. N. Boyko ◽  
M. V. Melnikov ◽  
O. V. Boyko ◽  
A. R. Kabaeva ◽  
M. A. Omarova ◽  
...  

According to numerous studies, gut microbiota plays a significant role in multiple sclerosis (MS) development. However, data on changes in the gut microbiota in MS is often contradictory. The most common approach in gut microbiota research is the 16S ribosomal RNA sequencing of fecal microbiota. However, such data do not reflect the composition of the entire body microbiota. There is also a lack of data on microbiota markers in the cerebrospinal fluid (CSF) of patients with MS and predisposing conditions.Objective: to assess the level of microbial markers in the CSF of patients with MS and radiologically isolated syndrome (RIS).Patients and methods. We used gas chromatography-mass spectrometry (GC-MS) to evaluate microbial markers levels in eight patients with MS, five patients with RIS, and seven controls.Results and discussion. We found an increase in microbial load in patients with MS, indicating a possible association of MS with polymicrobial infection. In particular, an increase in the content of Streptococcus markers was observed, as well as a tendency to a three-fold increase in the campesterol content (a marker of campesterol-producing microfungi) in the CSF of patients with MS, compared to the control group (diagnostic punctures, various diseases of the nervous system of a non-autoimmune or inflammatory nature, not acute states).Conclusion. GC-MS of microbial markers can be used to assess the presence of microbial markers in the CSF. The CSF of patients with MS contains an increased amount of various microbial markers, which may indicate a possible association of MS with polymicrobial infection.


Author(s):  
Wed Alluhaim ◽  
Manal M. Alkhulaifi ◽  
Godfred A. Menezes

Microbiota is the summation of all microorganisms living in the body. The alteration in microbiota can lead to chronic diseases, however; colonization with different commensal bacteria can correct these deficits. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by inadequate communication skills and social withdrawal and its etiology is uncertain. Typical gastrointestinal (GI) disorders symptoms are associated with ASD, in a prevalence range from 23% to 70%. The method of communication between the brain and the gut microbiota is likely the microbiota-gut-brain axis. Therefore, intervention studies have been published based on the use of prebiotics, probiotics and fecal microbiota transplantation (FMT). In this review, the possible correlation between gut microbiota and ASD is demonstrated. Additionally, how probiotics and microbial fecal microbiota transplantation (FMT) could modulate the gut microbiota and might represent a potential therapy for patients with ASD. Nearly all the GI functions postulated to be affected in ASD are improved by probiotics in animal studies. (FMT) ensures the transfer of several hundred bacterial strains, as opposed to probiotic therapy where only certain bacterial strains are supplemented. For ASD patients with dysbiosis, FMT is an interesting new therapeutic choice that could be considered.


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