Bifidobacteria-derived exopolysaccharide promotes anti-tumor immunity.

While several phylogenetically distinct bacterial taxa can predict responses to or improve cancer immunotherapies, the underlying mechanisms remain poorly understood. The use of microbes for microbial therapeutics is currently under intense research, yet safety and regulatory hurdles remain challenging. Thus, non-replicative bacterial-derived molecules or extracts provide promising alternatives.

Innate immune system signaling and intestinal dendritic cells migration to the brain underlie behavioral changes after microbial colonization in adult mice.

Background And Aims: Accumulating evidence suggests the microbiota is a key factor in Disorders of Gut-Brain Interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization.

T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota.

How the gut microbiota and immune system maintain intestinal homeostasis in concert with the enteric nervous system (ENS) remains incompletely understood. To address this gap, we assessed small intestinal transit, enteric neuronal density, enteric neurogenesis, intestinal microbiota, immune cell populations and cytokines in wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF and segmented filamentous bacteria (SFB)-monocolonized mice. SPF microbiota increased small intestinal transit in a T cell-dependent manner.

Early life microbiota colonization programs nociceptor sensitivity by regulating NGF production in mast cells.

Recent evidence suggests that the gut microbiota can influence pain sensitivity, highlighting the potential for microbiota-targeted pain interventions. During early life, both the microbiota and nociceptors are fine-tuned and respond to environmental factors, however, little is known about how they interact with each other. Using germ-free and gnotobiotic models, we demonstrate that microbiota colonization controls nociceptor sensitivity, partly by modulating mast cell production of nerve growth factor (NGF).

Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.

Background: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.

Early life microbiome influences on development of the mucosal innate immune system.

The gut microbiota is well known to possess immunomodulatory capacities, influencing a multitude of cellular signalling pathways to maintain host homeostasis. Although the formation of the immune system initiates before birth in a sterile environment, an emerging body of literature indicates that the neonatal immune system is influenced by a first wave of external stimuli that includes signals from the maternal microbiota. A second wave of stimulus begins after birth and must be tightly regulated during the neonatal period when colonization of the host occurs concomitantly with the maturation of the immune system, requiring a fine adjustment between establishing tolerance towards the commensal microbiota and preserving inflammatory responses against pathogenic invaders.

Microbes and vitamin D aid immunotherapy.

Vitamin D modulates intestinal epithelial cell function to enhance antitumor microbes.

Interaction of microbiota, mucosal malignancies, and immunotherapy-Mechanistic insights.

The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria.

Vascular traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk.

During bloodstream infections, neutrophils home to the liver as part of an intravascular immune response to eradicate blood-borne pathogens, but the mechanisms regulating this crucial response are unknown. Using in vivo imaging of neutrophil trafficking in germ-free and gnotobiotic mice, we demonstrate that the intestinal microbiota guides neutrophil homing to the liver in response to infection mediated by the microbial metabolite D-lactate. Commensal-derived D-lactate augments neutrophil adhesion in the liver independent of granulopoiesis in bone marrow or neutrophil maturation and activation in blood.

Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis.

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC).

Microbial metabolites and immunotherapy: Basic rationale and clinical indications.

Our microbiota has a critical role in shaping host immunity. Microbes that reside in the gut harbor a large metabolic arsenal to aid in physiological functions of the host. Microbial metabolites, which are products of microbial metabolism, such as short chain fatty acids (SCFA), purine metabolites, cyclic dinucleotides, tryptophan derivatives, and secondary bile acids, can tailor the host immune cell landscape in homeostasis and during cancer immunotherapy.

Microbiota alters the metabolome in an age- and sex- dependent manner in mice.

Commensal bacteria are major contributors to mammalian metabolism. We used liquid chromatography mass spectrometry to study the metabolomes of germ-free, gnotobiotic, and specific-pathogen-free mice, while also evaluating the influence of age and sex on metabolite profiles. Microbiota modified the metabolome of all body sites and accounted for the highest proportion of variation within the gastrointestinal tract.

Dysbiosis of a microbiota-immune metasystem in critical illness is associated with nosocomial infections.

Critically ill patients in intensive care units experience profound alterations of their gut microbiota that have been linked to a high risk of hospital-acquired (nosocomial) infections and adverse outcomes through unclear mechanisms. Abundant mouse and limited human data suggest that the gut microbiota can contribute to maintenance of systemic immune homeostasis, and that intestinal dysbiosis may lead to defects in immune defense against infections. Here we use integrated systems-level analyses of fecal microbiota dynamics in rectal swabs and single-cell profiling of systemic immune and inflammatory responses in a prospective longitudinal cohort study of critically ill patients to show that the gut microbiota and systemic immunity function as an integrated metasystem, where intestinal dysbiosis is coupled to impaired host defense and increased frequency of nosocomial infections.

From germ-free to wild: modulating microbiome complexity to understand mucosal immunology.

The gut microbiota influences host responses at practically every level, and as research into host-microbe interactions expands, it is not surprising that we are uncovering similar roles for the microbiota at other barrier sites, such as the lung and skin. Using standard laboratory mice to assess host-microbe interactions, or even host intrinsic responses, can be challenging, as slight variations in the microbiota can affect experimental outcomes. When it comes to designing and selecting an appropriate level of microbial diversity and community structure for colonization of our laboratory rodents, we have more choices available to us than ever before.

Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.

Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity.

Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization.

The intestine harbors a large population of resident eosinophils, yet the function of intestinal eosinophils has not been explored. Flow cytometry and whole-mount imaging identified eosinophils residing in the lamina propria along the length of the intestine prior to postnatal microbial colonization. Microscopy, transcriptomic analysis, and mass spectrometry of intestinal tissue revealed villus blunting, altered extracellular matrix, decreased epithelial cell turnover, increased gastrointestinal motility, and decreased lipid absorption in eosinophil-deficient mice.

Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.

The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy.

Method for absolute quantification of short chain fatty acids via reverse phase chromatography mass spectrometry.

Short chain fatty acids (SCFAs; including acetate, propionate, and butyrate) are an important class of biological molecules that play a major role in modulating host-microbiome interactions. Despite significant research into SCFA-mediated biological mechanisms, absolute quantification of these molecules in their native form by liquid chromatography mass spectrometry is challenging due to their relatively poor chromatographic properties. Herein, we introduce SQUAD, an isotope-based strategy for absolute quantification of SCFAs in complex biological samples.

Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.

Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with β-glucan (HFS/OB), resistant starch (HFS/OR), or β-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function.

Crohn's disease therapeutic dietary intervention (CD-TDI): study protocol for a randomised controlled trial.

Introduction: Dietary patterns that might induce remission in patients with active Crohn's disease (CD) are of interest to patients, but studies are limited in the published literature. We aim to explore the efficacy of the CD therapeutic dietary intervention (CD-TDI), a novel dietary approach developed from best practices and current evidence, to induce clinical and biomarker remission in adult patients with active CD.

Methods And Analysis: This study is a 13-week, multicentre, randomised controlled trial in patients with mild-to-moderate active CD at baseline.

Microbiota regulates intratumoral monocytes to promote anti-tumor immune responses.

The gut microbiota has been shown to promote the efficacy of cancer therapy through regulating adaptive immune responses. In this issue of Cell, Lam et al. provide new evidence demonstrating that specific gut bacteria also reprogram the innate immune tumor microenvironment to enhance the efficacy of cancer therapies.

Distinct microbial communities colonize tonsillar squamous cell carcinoma.

Squamous cell carcinoma of the tonsil is one of the most frequent cancers of the oropharynx. The escalating rate of tonsil cancer during the last decades is associated with the increase of high risk-human papilloma virus (HR-HPV) infections. While the microbiome in oropharyngeal malignant diseases has been characterized to some extent, the microbial colonization of HR-HPV-associated tonsil cancer remains largely unknown.

Microbiota and Microglia Interactions in ASD.

Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis.