Biogeographical distribution of gut microbiome composition and function is partially recapitulated by fecal transplantation into germ-free mice.

Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities.

Stress-Resilience Impacts Psychological Wellbeing: Evidence from Brain-Gut Microbiome Interactions.

The brain-gut-microbiome (BGM) system plays an influential role on mental health. We characterized BGM patterns related to resilience using fecal samples and multimodal MRI. Data integration analysis using latent components showed the high resilience phenotype was associated with lower depression and anxiety symptoms, higher frequency of bacterial transcriptomes (related to environmental adaptation, genetic propagation, energy metabolism, anti-inflammation), increased metabolites (N-acetylglutamate; dimethylglycine), and cortical signatures (increased resting state functional connectivity between reward circuits and sensorimotor networks; decreased grey matter volume and white matter tracts within the emotion regulation network).

Experiences of discrimination are associated with microbiome and transcriptome alterations in the gut.

Background: Discrimination is a recognized psychosocial stressor that has been linked to various negative health outcomes. This study explored the impact of discrimination on gut health, specifically focusing on microbiome changes, predicted metagenomic differences, transcriptomic profiles, and the potential for using a multi-omic approach to predict discrimination to identify discrimination status for an individual. Methods: We conducted a comprehensive investigation involving male and premenopausal female participants, using the Everyday Discrimination Scale to classify them into either high or low discrimination.

Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation.

Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS).

Sex Differences in Colonic Mucosal Microbiome of Irritable Bowel Syndrome Patients Compared to Healthy Controls.

Background: Irritable bowel syndrome (IBS) is a female-predominant disorder of brain-gut interactions. Our previous study on colonic mucosal microbiota demonstrated significant differences between IBS bowel habit subtypes and showed that gut microbiota is associated with abdominal pain in IBS patients. However, there is no consensus on sex-related differences in mucosal microbiota in IBS compared to healthy controls (HC).

Differential brainstem connectivity according to sex and menopausal status in healthy men and women.

Background Brainstem nuclei play a critical role in both ascending monoaminergic modulation of cortical function and arousal, and in descending bulbospinal pain modulation. Even though sex-related differences in the function of both systems have been reported in animal models, a complete understanding of sex differences, as well as menopausal effects, in brainstem connectivity in humans is lacking. This study evaluated resting-state connectivity of the dorsal raphe nucleus (DRN), right and left locus coeruleus complex (LCC), and periaqueductal gray (PAG) according to sex and menopausal status in healthy individuals.

Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research.

Validation of a Machine Learning Algorithm, EVendo, for Predicting Esophageal Varices in Hepatocellular Carcinoma.

Background: Treatment with atezolizumab and bevacizumab has become standard of care for advanced unresectable hepatocellular carcinoma (HCC) but carries an increased gastrointestinal bleeding risk. Therefore, patients are often required to undergo esophagogastroduodenoscopy (EGD) to rule out esophageal varices (EV) prior to initiating therapy, which can delay care and lead to unnecessary procedural risks and health care costs. In 2019, the EVendo score was created and validated as a noninvasive tool to accurately screen out patients who were at low risk for having EV that required treatment.

Enhanced CTLA-4 blockade anti-tumor immunity with APG-157 combination in a murine head and neck cancer.

Background: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors.

Methods: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies.

Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms.

Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown.

Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms.

Advances in Brain-Gut-Microbiome Interactions: A Comprehensive Update on Signaling Mechanisms, Disorders, and Therapeutic Implications.

The complex, bidirectional interactions between the brain, the gut, and the gut microbes are best referred to as the brain gut microbiome system. Animal and clinical studies have identified specific signaling mechanisms within this system, with gut microbes communicating to the brain through neuronal, endocrine, and immune pathways. The brain, in turn, modulates the composition and function of the gut microbiota through the autonomic nervous system, regulating gut motility, secretion, permeability, and the release of hormones impacting microbial gene expression.

Subchronic inhalation exposure to ultrafine particulate matter alters the intestinal microbiome in various mouse models.

Exposure to ultrafine particles (UFPs) has been associated with multiple adverse health effects. Inhaled UFPs could reach the gastrointestinal tract and influence the composition of the gut microbiome. We have previously shown that oral ingestion of UFPs alters the gut microbiome and promotes intestinal inflammation in hyperlipidemic Ldlr mice.

Mg and the microbiome: A liver-protective duo.

Acute liver failure continues to carry high morbidity and mortality with limited therapeutic options. In this issue of Cell Host & Microbe, Li et al. demonstrate that oral magnesium can protect against acetaminophen-induced liver injury through alterations in the microbiome.

Discrimination exposure impacts unhealthy processing of food cues: crosstalk between the brain and gut.

Experiences of discrimination are associated with adverse health outcomes, including obesity. However, the mechanisms by which discrimination leads to obesity remain unclear. Utilizing multi-omics analyses of neuroimaging and fecal metabolites, we investigated the impact of discrimination exposure on brain reactivity to food images and associated dysregulations in the brain-gut-microbiome system.

Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel.

Importance: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.

Objective: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.

Predictive Algorithm for Hepatic Steatosis Detection Using Elastography Data in the Veterans Affairs Electronic Health Records.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS).

Microbiota-Dependent Upregulation of Bitter Taste Receptor Subtypes in the Mouse Large Intestine in High-Fat Diet-Induced Obesity.

Bitter taste receptors (Tas2rs in mice) detect bitterness, a warning signal for toxins and poisons, and are expressed in enteroendocrine cells. We tested the hypothesis that Tas2r138 and Tas2r116 mRNAs are modulated by microbiota alterations induced by a long-term high-fat diet (HFD) and antibiotics (ABX) (ampicillin and neomycin) administered in drinking water. Cecum and colon specimens and luminal contents were collected from C57BL/6 female and male mice for qRT-PCR and microbial luminal 16S sequencing.

Evaluation of and implications for a novel hepatitis C e-consult direct-to-treatment pilot program.

A Hepatitis C (HCV) e-Consult Direct-To-Treatment (DTT) program managed by midlevel providers was developed at the Veteran Affairs Greater Los Angeles Healthcare System (VAGLAHS) which provided remote referral and, in some, remote management of HCV. DTT patients were more likely to be initiated on HCV treatment compared to standard of care (SOC), lending support for similar programs of remote engagement in HCV care.

Mediation of the association between disadvantaged neighborhoods and cortical microstructure by body mass index.

Background: Living in a disadvantaged neighborhood is associated with worse health outcomes, including brain health, yet the underlying biological mechanisms are incompletely understood. We investigated the relationship between neighborhood disadvantage and cortical microstructure, assessed as the T1-weighted/T2-weighted ratio (T1w/T2w) on magnetic resonance imaging, and the potential mediating roles of body mass index (BMI) and stress, as well as the relationship between trans-fatty acid intake and cortical microstructure.

Methods: Participants comprised 92 adults (27 men; 65 women) who underwent neuroimaging and provided residential address information.

The Association Between a Mediterranean Diet and Symptoms of Irritable Bowel Syndrome.

Background & Aims: Low adherence to Mediterranean diet (MD) has been shown to be associated with a higher prevalence of irritable bowel syndrome (IBS), but its association with IBS symptoms is not established. We aim to assess the association between MD and IBS symptoms, identify components of MD associated with IBS symptoms, and determine if a symptom-modified MD is associated with changes in the gut microbiome.

Methods: One hundred and six Rome +IBS and 108 health control participants completed diet history and gastrointestinal symptom questionnaires.