Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis

Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients

Atopic dermatitis and food sensitization in South African toddlers: Role of fiber and gut microbiota

The pathogenesis of atopic dermatitis (AD) is complex and related to allergic responses and defects in skin barrier function. In common with many atopic diseases, the prevalence of AD has been increasing across the world.1 One of the theories for this increase is increased hygiene and urbanization-related changes in the environment, which can affect the human microbiome.2 Previous studies have found associations between the composition of the early gut microbiome and development of atopic conditions, including AD.3 Although the rate of atopic conditions, including AD and food allergy, is increasing on all continents, the prevalence of these diseases is still lower in African countries.1 This is especially interesting because individuals of African origin who live in Western countries, such as African Americans, are at a higher risk for severe AD.4 This variation places Africa in a special position; studying African populations is necessary not only to find ways to prevent increases of allergy conditions in African countries but also to provide important clues to the causes of this global increasing of allergic conditions. Young children who have developed AD in African communities with a low incidence of atopic disease might be the transitional group. In the current study, we have, for the first time to our knowledge, analyzed the fecal microbiota composition of a group of young black African children aged 12 to 36 months old with and without AD living in the same community in Cape Town, South Africa. Our primary goal was to examine whether toddlers with AD and control toddlers from Cape Town have different microbiomes in terms of bacterial richness and diversity. We also aimed to investigate the differences in the relative abundance for different operational taxonomic units between these 2 groups. In our subgroup analyses, we further tested the effect of multiple environmental factors on the gut microbiome in these children

Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles.</p> <p>Methods</p> <p>We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4kD dextran was measured at 48 hours.</p> <p>Results</p> <p>PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice.</p> <p>Conclusions</p> <p>Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut <it>in vitro </it>and <it>in vivo</it>. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.</p

Sialylation and fucosylation modulate inflammasome-activating eIF2 Signaling and microbial translocation during HIV infection

An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of several comorbidities. We examined terminal ileum, right colon, and sigmoid colon biopsies from HIV-infected virally-suppressed individuals and found that gut glycomic patterns are associated with distinct microbial compositions and differential levels of chronic inflammation and HIV persistence. In particular, high levels of the pro-inflammatory hypo-sialylated T-antigen glycans and low levels of the anti-inflammatory fucosylated glycans were associated with higher abundance of glycan-degrading microbial species (in particular, Bacteroides vulgatus), a less diverse microbiome, higher levels of inflammation, and higher levels of ileum-associated HIV DNA. These findings are linked to the activation of the inflammasome-mediating eIF2 signaling pathway. Our study thus provides the first proof-of-concept evidence that a previously unappreciated factor, gut glycosylation, is a force that may impact the vicious cycle between HIV infection, microbial translocation, and chronic inflammation

Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis

Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients

Raw Milk-Induced Protection against Food Allergic Symptoms in Mice Is Accompanied by Shifts in Microbial Community Structure

The mechanism underlying the allergy-protective effects of raw cow's milk is still unknown, but the modulation of the gut microbiome may play a role. The effects of consuming raw cow's milk or processed milk on fecal microbial communities were therefore characterized in an experimental murine model. C3H/HeOuJ mice were treated with raw milk, pasteurized milk, skimmed raw milk, pasteurized milk supplemented with alkaline phosphatase (ALP), or phosphate-buffered saline (PBS) for eight days prior to sensitization and challenge with ovalbumin (OVA). Fecal samples were collected after milk exposure and after OVA sensitization, and microbiomes were characterized using 16S ribosomal RNA gene amplicon sequencing. Treatment with raw milk prior to OVA sensitization increased the relative abundance of putative butyrate-producing bacteria from the taxa Lachnospiraceae UCG-001, Lachnospiraceae UCG-008, and Ruminiclostridium 5 (Clostridial clusters XIVa and IV), while it decreased the relative abundance of Proteobacterial genera such as Parasutterella, a putative pro-inflammatory bacterial genus. This effect was observed after eight days of raw milk exposure and became more pronounced five weeks later, after allergic sensitization in the absence of milk. Similar trends were observed after treatment with skimmed raw milk. Conversely, the feeding of pasteurized milk led to a loss of allergy protection and a putative dysbiotic microbiome. The addition of ALP to pasteurized milk restored the protective effect observed with raw milk and mitigated some of the microbial community alterations associated with milk pasteurization. Raw milk-induced protection against food allergic symptoms in mice is accompanied by an increased relative abundance of putative butyrate-producing Clostridiales and a decreased relative abundance of putative pro-inflammatory Proteobacteria. Given the safety concerns regarding raw milk consumption, this knowledge is key for the development of new, microbiologically safe, preventive strategies to reduce the incidence of allergic diseases