Emerging evidence linking the gut microbiome to neurologic disorders

The gut microbiome contributes to the development and function of the immune, metabolic, and nervous systems. Furthermore, commensal bacteria modulate symptoms and pathology in mouse models of neuropsychiatric and neurodevelopmental diseases. Uncovering mechanisms that are utilized by the microbiome to mediate gut–brain connections may provide novel opportunities to target therapies to the gut in order to treat neurologic disorders

Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis

The gastrointestinal (GI) tract contains much of the body’s serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis.</p

Emerging evidence linking the gut microbiome to neurologic disorders

Editorial summary The gut microbiome contributes to the development and function of the immune, metabolic, and nervous systems. Furthermore, commensal bacteria modulate symptoms and pathology in mouse models of neuropsychiatric and neurodevelopmental diseases. Uncovering mechanisms that are utilized by the microbiome to mediate gut–brain connections may provide novel opportunities to target therapies to the gut in order to treat neurologic disorders

Disseminated Fusarium infection in autologous stem cell transplant recipient

Disseminated infection by Fusariumis a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusariuminfection in an autologous bone marrow transplant recipient during pre-engraftment phase

Household Food Insecurity, Anemia, Malnutrition and Unfavorable Dietary Diversity among Adolescents: Quadruple Whammies in the Era of Escalating Crises in Lebanon

Adolescence is a transitional period between childhood and adulthood. Nowadays, adolescents in Lebanon are growing during a time of unprecedented health crises and political instability. This study aimed to determine the prevalence and correlates of malnutrition, dietary diversity in adolescents&rsquo; households, and adolescents&rsquo; self-reported food insecurity in Lebanon. A national representative sample of 450 parent&ndash;adolescent dyads (parents: mean age &plusmn; standard deviation (SD) = 46.0 &plusmn; 7.0, mothers: 59.0%; adolescents: mean age &plusmn; SD = 15.0 &plusmn; 3.0, girls: 54.6%) were interviewed. Anthropometric and blood hemoglobin measurements were performed for adolescents. The Food Consumption Score, the Arab Family Food Security Scale and the Adolescent-Level Food-Security Scale were used. The overall prevalence of adolescent stunting, thinness, overweight, obesity and anemia was 6.7%, 4.7%, 19.3%, 12.9% and 16.7%, respectively. Almost 40.4% and 68% of adolescent&rsquo;s households consumed undiversified diets and were food insecure, respectively. Food insecurity (FI) affected 54.0% of adolescents. Adolescents attending schools (vs. university) were eight times more likely to be stunted (p = 0.04). Boys had a 4.3 times higher thinness risk (p = 0.005) compared to girls. Households reporting an income decline since the start of the Lebanese economic crisis were three times more likely to have a thin adolescent (p = 0.01). Parental overweight/obesity (p = 0.002) and lower education level (p = 0.04) nearly doubled the risk of adolescent overweight or obesity. At a time when escalating crises in Lebanon are shifting diets for the youngest generations, the development of adolescent-responsive nutritional policies becomes a must