Recent Publications
- Antibiotics are believed to affect host physiology by altering the gut microbiota. However, it remains unclear which effects of antibiotics are microbiota dependent and which are microbiota independent. Here we present a resource encompassing host and microbiota responses to antibiotic treatment and a computational tool with which to analyse them. Metagenomic and transcriptomic analyses of conventional and germ-free mice revealed that antibiotic administration routes and their combinations…
- CONCLUSIONS: Perturbations in dietary, ileal, microbial, and metabolic signatures persist during CD remission despite advanced, effective immune treatments. These findings likely underline the remitting-relapsing nature of CD and suggest that interventions targeting diet, epithelial health, and microbial and metabolic functions may promote deeper, longer-lasting remission states.
- Macrophage-toxic bacteria from patients with ulcerative colitis worsen gut inflammation in mice.
- Autophagy is an evolutionarily conserved cellular process that is prominent during bacterial infections. In this review article, we discuss how direct pathogen clearance via xenophagy and regulation of inflammatory products represent dual functions of autophagy that coordinate an effective antimicrobial response. We detail the molecular mechanisms of xenophagy, including signals that indicate the presence of an intracellular pathogen and autophagy receptor-mediated cargo targeting, while…
- Autophagy is a key innate immune defense mechanism in intestinal epithelial cells. Bacterial invasion of epithelial cells activates antibacterial autophagy through a process that requires the innate immune adaptor protein MYD88, yet how MYD88 signaling connects to the autophagy machinery is unknown. Here, we show that the mouse intestinal pathogen Salmonella enterica Serovar Typhimurium (Salmonella Typhimurium) triggers MYD88 signaling that regulates binding of the anti-autophagy factor B cell…
- Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer….
- Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection. Mice lacking IL-1β (IL-1β -/-) failed to recruit neutrophils to the gut during infection, which reduced tissue damage and prevented depletion of short-chain fatty acid…
- Autism is a neurodevelopmental disorder characterized by early-onset social behavioral deficits and repetitive behaviors. Chromodomain helicase DNA-binding protein (CHD8) is among the genes most strongly associated with autism. In addition to the core behavioral symptoms of autism, affected individuals frequently present with gastrointestinal symptoms that are also common among individuals harboring mutations in the gene encoding CHD8. However, little is known regarding the mechanisms whereby…
- Intestinal epithelial cells form the largest barrier in the body, separating us from the outside world. Here, we review recent findings that highlight the role of autophagy in the cell-intrinsic response of the epithelial cells to the harsh intestinal environment and how they shape host physiology.
- Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn produce a thicker and less penetrable mucus barrier. Pharmacological reduction of the ER stress or activation of the unfolded protein response (UPR) in…
- Colonic goblet cells are specialized epithelial cells that secrete mucus to physically separate the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 enables the production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, genetically inhibiting Beclin 1-induced autophagy…
- Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a…
- No abstract
- Metabolic plasticity is a hallmark of the ability of metastatic cancer cells to survive under stressful conditions. The intracellular Fer kinase is a selective constituent of the reprogramed mitochondria and metabolic system of cancer cells. In the current work, we deciphered the modulatory roles of Fer in the reprogrammed metabolic systems of metastatic, lung (H358), non-small cell lung cancer (NSCLC), and breast (MDA-MB-231), triple-negative breast cancer (TNBC), carcinoma cells. We show that…
- In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy,…