Eric M Brown

Eric M Brown
Broad Institute of MIT and Harvard

PhD in Microbiology and Immunology

About

35
Publications
16,468
Reads
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3,185
Citations
Additional affiliations
May 2011 - April 2017
University of British Columbia - Vancouver
Position
  • PhD Student

Publications

Publications (35)
Article
The intestinal microbiota plays a crucial role in influencing the development of host immunity, and in turn the immune system also acts to regulate the microbiota through intestinal barrier maintenance and immune exclusion. Normally, these interactions are homeostatic, tightly controlled, and organized by both innate and adaptive immune responses....
Article
Intestinal adaptive immune responses influence host health, yet only a few intestinal bacteria species that induce cognate adaptive immune responses during homeostasis have been identified. Here, we show that Akkermansia muciniphila , an intestinal bacterium associated with systemic effects on host metabolism and PD-1 checkpoint immunotherapy, indu...
Article
Immunoglobulin (Ig) A controls host-microbial homeostasis in the gut. IgA recognition of beneficial bacteria is decreased in acutely undernourished children, but the factors driving these changes in IgA targeting are unknown. Child undernutrition is a global health challenge that is exacerbated by poor sanitation and intestinal inflammation. To und...
Article
Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical is...
Article
Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipi...
Preprint
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SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development of neutralizing antibodies generally correlated with protection against reinfection. Here, we have characterized both neutralizing activity and T cell responses in a cluster of subjects with mild disease linked to a single spreading event. Surprisingl...
Preprint
Plasma cells (PCs) constitute a significant fraction of cells in colonic mucosa and contribute to inflammatory lymphocytic infiltrates in ulcerative colitis (UC). While gut PCs secrete 3-5 g of immunoglobulins daily, including IgA antibodies that target colitogenic bacteria, their role in UC is not known. Here, we combined B cell sorting with singl...
Article
Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG...
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The impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in infants and mothers with multiple parasitic infections. In this work, we studied the relationship between protist and helminth parasite colonization and the intestinal microbiota structure in an asy...
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Active inflammatory bowel disease (IBD) often coincides with increases of Ruminococcus gnavus , a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of R. gnavus to identify molecular mechanisms that would link R. gnavus to inflammation. Here, we show that on...
Article
Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract SARS-CoV-2 and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA-seq and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct...
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The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied...
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Nonalcoholic fatty liver disease (NAFLD) remains a global epidemic, but it is often studied in the context of obesity and aging. Nutritional deficits, however, also trigger hepatic steatosis, influencing health trajectories in undernourished pediatric populations. Here, we report that exposure to specific gut microbes impacts fatty liver pathology...
Preprint
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Around 3.5 billion people are colonized by intestinal parasites worldwide. Intestinal parasitic eukaryotes interact not only with the host, but also with the intestinal microbiota. In this work, we studied the relationship between the presence of multiple enteric parasites and the community structure of the bacterial and eukaryote intestinal microb...
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Identifying immunodominant T cell epitopes remains a significant challenge in the context of infectious disease, autoimmunity, and immuno-oncology. To address the challenge of antigen discovery, we developed a quantitative proteomic approach that enabled unbiased identification of major histocompatibility complex class II (MHCII)–associated peptide...
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Background: Globally one out of four children under 5 years is affected by linear growth delay (stunting). This syndrome has severe long-term sequelae including increased risk of illness and mortality and delayed psychomotor development. Stunting is a syndrome that is linked to poor nutrition and repeated infections. To date, the treatment of stun...
Article
Blastocystis is the most prevalent protist of the human intestine, colonizing approximately 20% of the North American population and up to 100% in some nonindustrialized settings. Blastocystis is associated with gastrointestinal and systemic disease but can also be an asymptomatic colonizer in large populations. While recent findings in humans have...
Article
The relative contributions of innate and adaptive immune mechanisms in responding to the intestinal microbiota during ontogeny are largely unknown. A recent study in Nature by Mao et al. (2018) elegantly dissects the role of each cell type in the intestine and further describes the metabolic cost to innate immunity. The relative contributions of in...
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Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction...
Article
There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model...
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Importance: Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica...
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Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we...
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Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their health status as well as their immune system. An ever-expanding number of articles...
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Studies of the relationship between the microbiome and the development and function of the immune system are demonstrating novel concepts that could significantly alter the way we treat disease and promote wellness. Several diseases, including inflammatory bowel disease, allergy/asthma, and diabetes, are associated with changes in composition of th...
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A conference entitled ‘Human microbiome science: Vision for the future’ was organized in Bethesda, MD from July 24 to 26, 2013. The event brought together experts in the field of human microbiome research and aimed at providing a comprehensive overview of the state of microbiome research, but more importantly to identify and discuss gaps, challenge...
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To augment capacity-building for microbiome and probiotic research in Africa, a workshop was held in Nairobi, Kenya, at which researchers discussed human, animal, insect, and agricultural microbiome and probiotics/prebiotics topics. Five recommendations were made to promote future basic and translational research that benefits Africans.
Article
Mucus production by goblet cells of the large intestine serves as a crucial antimicrobial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. Here, we demonstrate that the NLR...
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The mammalian intestinal tract harbors a diverse community of trillions of microorganisms, which have co-evolved with the host immune system for millions of years. Many of these microorganisms perform functions critical for host physiology, but the host must remain vigilant to control the microbial community so that the symbiotic nature of the rela...
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Susceptibility of a particular species to prion disease is affected by small differences in the sequence of PrP and correlates with the propensity of its PrP to assume the β-state. A helix-cap motif in the β2-α2-loop of native α-helical rabbit PrP, a resistant species, contains sequence differences that influence intra- and interspecies transmissio...
Data
Full-text available
2FO-FC electron density map at 1.5δ overlaid on the β2−α2 loops from respective structures of (A) wild-type rabbit PrP 121–230 (B) S170N mutant rabbit PrP 121–230, (C) S174N mutant rabbit PrP 121–230 and (D) S170N/S174N mutant rabbit. (PDF)
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Background Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy do...
Article
The composition and role of bacteria in the human gut has been studied intensely and is a burgeoning field of scientific research. However, there is a relative lack of research on other microorganisms which compose our gut flora such as bacteriophage, archaea and fungi. The aim of our study was to begin to fill this gap. The archaeal, fungal and ba...

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