NEWS AND EVENTS
RECENT AWARDS. The Xavier lab has recently been awarded funding from FARE (Food Allergy Research & Education) and ASAP (Aligning Science Across Parkinson's) to support their work on understanding the role of neuroimmune interactions in allergen sensing pathways and Parkinson’s disease, respectively.
A unique community of gut microbes in centenarians may help support longevity. In a collaboration with Kenya Honda’s lab to characterize gut microbiomes of 160 Japanese centenarians, the Xavier lab found that, compared to younger people, the centenarians showed higher levels of intestinal microbes that produce secondary bile acids such as isoalloLCA, which strongly inhibits the growth of some gram-positive bacteria - see the news story. Their findings, published in Nature, could help researchers uncover mechanisms and biomarkers of healthy aging, and develop new ways to treat chronic inflammation and bacterial disease.
Identifying multiomic markers of IBD treatment response. It is difficult to predict response to treatment for inflammatory bowel disease (IBD) because of the complexity of the intestinal microbiome and the lack of predictive biomarkers. In a study published in Cell Host & Microbe, Jonathan Wei Jie Lee and Damian Plichta in the Xavier lab and colleagues profiled stool and blood samples from patients with IBD before treatment and tracked treatment response. They used modeling and machine learning to identify metagenomic, metabolomic, and proteomic markers that could predict which patients would achieve remission. Biomarkers varied by therapy class, with microbial diversity in the gut being a strong indicator of anti-cytokine therapy success. These response markers could lead to better IBD treatment selection.
Counter-regulation of lipid membrane dynamics during xenophagy modulates an innate defense response. Despite the importance of membrane identity and trafficking in selective autophagy, the role of lipid membrane composition remains largely unknown. In a study out in Cell Reports, Kai Liu and colleagues in the Xavier lab identified the PI(4)P phosphatase SAC1 as an essential regulator of xenophagy during Salmonella infection. Loss of SAC1 activity delays fusion between Salmonella-containing autophagosomes and lysosomes, leading to increased intracellular bacterial replication. They additionally found that the Salmonella type III secreted effector and PI(4)P-binding protein, SteA, promotes replication by impeding lysosomal fusion.
Type 1 diabetes could become a preventable disease pending clinical trials with B. infantis. An upcoming clinical study will test whether @EvolveBio B. infantis probiotic can prevent the development of type 1 diabetes in genetically predisposed infants - see the news story. DIABIMMUNE was one of the key studies that clearly associated gut microbiota with the development of type 1 diabetes. In this study, scientists collected stool samples from children living in Finland, Russian Karelia, and Estonia from birth to 3 years of age. Though they share a border, children growing up in Finland and Russian Karellia grow up in very different environments. Higher levels of modernization in Finland coincide with higher incidence of type 1 diabetes and other automiimune diseases. The stark contrasts in the microbiota of the DIABIMMUNE children was first reported by Tommi Vatanen, a computational biologist and microbiologist in the Xavier lab.
The enteric nervous system as a hub for intestinal and immune cell crosstalk. Studying enteric neurons is a challenge because they are rare, fragile, and not easy to isolate from surrounding tissue. A team led by Ramnik Xavier and Aviv Regev devised two new methods to study the ENS in mice and humans at single-cell resolution: RAISIN RNA-seq and MIRACL-seq. Together, these techniques enabled the team to infer that neurons in the gut are communicating with a variety of other cell types, including immune cells. They also found that key genes associated with disease are expressed in the ENS. Read more in a Broad news story.
Gut bacteria that metabolize cholesterol may have a positive impact on people's cardiac health. In a study published in Cell Host and Microbe, the Xavier lab found that people who have cholesterol metabolizing bacteria in their intestines have lower cholesterol levels in their blood than those without the microbes. The discovery suggests a possible reason why some people can consume more cholesterol in their diet with minimal effect on their blood cholesterol levels. It also hints that boosting populations of these bacteria, through diet, probiotics, or another kind of treatment, may one day be an effective way to help lower cholesterol levels.
Therapeutic opportunities in inflammatory bowel disease: mechanistic dissection of host-microbiome relationships. Mechanistic and functional links between host-microbiome interplay and irritable bowel disease pathology are building and presenting exciting but challenging opportunities to manipulate the microbiome for therapeutic benefit. A summary of the review is available here.
Gut sphingolipids send signals about health and disease. Sphingolipids, a signaling molecule and structural component of both bacterial and mammalian cell membranes, play a central role in regulating inflammation, immunity, growth, and cell survival. To date, the specific roles of bacterial sphingolipids in regulating innate immunity or metabolism in the mammalian gut have been largely unknown. Reporting in Cell Host & Microbe, Eric Brown, Ramnik Xavier, Hera Vlamakis, Clary Clish and colleagues describe sphingolipid metabolite alterations in stool as a defining signature in inflammatory bowel disease in humans and further demonstrate in mice that bacterial sphingolipid production plays a significant role in the host’s gut health and disease.
Eavesdropping on gut gossip. The gut's intestinal stem cells (ISCs) "talk" to other cell types to help maintain a robust and healthy cellular community. In this week's Cell, Moshe Biton, Adam Haber, Noga Rogel, Aviv Regev, Ramnik Xavier, and colleagues dive into one such conversation, between ISCs and T helper (Th) cells. They found that some ISCs express MCH II (a surface complex that activates Th cells), while Th cells produce cytokines (chemical messages) that influence ISCs’ behavior. The crosstalk may help maintain the right balance of immune activity in the gut, as well as a hardy stem cell pool. Read more in a Broad news story.
Peptide presentation prognosticator produced. We don't fully understand the immune system's rules for determining whether a peptide from a bacterium and other source will 1) be presented to T cells, and 2) spark an immune response. To help bring new clarity, Dan Graham, Chengwei Luo, Ramnik Xavier, and colleagues profiled the "peptidome" of potential antigens bound to MHC class II (a protein complex that presents peptides to T cells) in mice. They used their data to build and train BOTA, a machine learning algorithm that predicts antigenic peptides based on bacterial whole genome data. Learn more in Nature Medicine and in a Broad news story. A comprehensive summary of the study can be found here.