Gut microbiota prevents small intestinal tumor formation due to bile acids in gnotobiotic mice.

The gut microbiota is implicated in the development of intestinal tumors. Furthermore, Western diet is a risk factor for colorectal cancer and induces alterations in both the microbiota and bile acid metabolism. Therefore, we aimed to investigate the causal role of Western diet-induced changes in the microbiota and secondary bile acid production, which were linked to disease exacerbation in pigs.

Protocol to study human gut bacterial communities and rhythmicity ex vivo using a chemostat system.

Chemostat systems can be used to cultivate complex intestinal microbial communities ex vivo. Here, we present a protocol to transfer bacteria from human fecal material into chemostat systems as well as settings to simulate infant or adult colonic conditions. We describe the experimental setup, media design, donor selection, 16S rRNA amplicon sequencing, and circadian analysis of bacterial abundance.

Histomorphological scoring of murine colitis models: A practical guide for the evaluation of colitis and colitis-associated cancer.

Background And Aims: Histomorphology is a powerful and cost-efficient tool for evaluating inflammatory and neoplastic conditions. Inflammatory bowel disease (IBD) is a widespread condition with globally rising incidences, and a lot of research is done to better understand the pathogenesis of IBD and to identify potential therapeutic approaches. However, standardized and reproducible scores for the histomorphological evaluation of murine IBD models are lacking.

Microbiota during pregnancy and early life: role in maternal-neonatal outcomes based on human evidence.

Here, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect.

Development of a Global Metabo-Lipid-Prote-omics Workflow to Compare Healthy Proximal and Distal Colonic Epithelium in Mice.

A multimetabo-lipid-prote-omics workflow was developed to characterize the molecular interplay within proximal (PC) and distal (DC) colonic epithelium of healthy mice. This multiomics data set lays the foundation to better understand the two tissue types and can be used to study, for example, colon-related diseases like colorectal cancer or inflammatory bowel disease. First, the methyl -butyl ether extraction method was optimized, so that from a single tissue biopsy >350 reference-matched metabolites, >1850 reference-matched lipids, and >4500 proteins were detected by using targeted and untargeted metabolomics, untargeted lipidomics, and proteomics.

Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease.

Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting the mitochondrial chaperone, heat shock protein 60 (Hsp60). This metabolic perturbation causes self-resolving tissue injury.

Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation.

The expression of clock genes has been observed to be impaired in biopsies from patients with inflammatory bowel disease (IBD). Disruption of circadian rhythms, which occurs in shift workers, has been linked to an increased risk of gastrointestinal diseases, including IBD. The peripheral circadian clock in intestinal epithelial cells (IECs) was previously shown to balance gastrointestinal homeostasis by regulating the microbiome.

Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition.

Background: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolization in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis.

The human intestinal bacterium influences gut metabolomes in gnotobiotic mice.

The intestinal microbiota and its metabolites are known to influence host metabolic health. However, little is known about the role of specific microbes. In this work, we used the minimal consortium Oligo-Mouse-Microbiota (OMM12) to study the function of under defined conditions in gnotobiotic mice.

Controversy on health-based guidance values for bisphenol A-the need of criteria for studies that serve as a basis for risk assessment.

Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range of HBGVs covers a considerable part of the range from highly toxic to relatively non-toxic substances. As such heterogeneity of regulatory opinions is a challenge not only for scientific risk assessment but also for all stakeholders, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) analyzed the reasons for the current discrepancy and used this example to suggest improvements for the process of HBGV recommendations.

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food.

Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation.

Diurnal rhythmicity of infant fecal microbiota and metabolites: A randomized controlled interventional trial with infant formula.

Microbiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk.

On the limits of 16S rRNA gene-based metagenome prediction and functional profiling.

Molecular profiling techniques such as metagenomics, metatranscriptomics or metabolomics offer important insights into the functional diversity of the microbiome. In contrast, 16S rRNA gene sequencing, a widespread and cost-effective technique to measure microbial diversity, only allows for indirect estimation of microbial function. To mitigate this, tools such as PICRUSt2, Tax4Fun2, PanFP and MetGEM infer functional profiles from 16S rRNA gene sequencing data using different algorithms.

Systematic Evaluation of Clinical, Nutritional, and Fecal Microbial Factors for Their Association With Colorectal Polyps.

Introduction: The identification of risk factors for precursor lesions of colorectal cancer (CRC) holds great promise in the context of prevention. With this study, we aimed to identify patient characteristics associated with colorectal polyps (CPs) and polyp features of potential malignant progression. Furthermore, a potential association with gut microbiota in this context was investigated.

The TNF∆ARE Model of Crohn's Disease-like Ileitis.

Crohn's disease (CD) is one of the 2 main phenotypes of inflammatory bowel diseases (IBDs); CD ischaracterized by a discontinuous, spontaneously recurring, transmural immunopathology that largely affects the terminal ileum. Crohn's disease exhibits both a relapsing and progressive course, and its prevalence is on the rise globally, mirroring the trends of industrialization. While the precise pathogenesis of CD remains unknown, various factors including immune cell dysregulation, microbial dysbiosis, genetic susceptibility, and environmental factors have been implicated in disease etiology.

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling.

Background & Aims: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC.

promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature.

Objective: infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between infection and colon cancer is lacking.

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease.

Background: Crohn's disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation.

Results: We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including Tnf and SAMP/Yit mice.

TNF ΔARE Pigs: A Translational Crohn's Disease Model.

Background And Aims: Crohn's disease [CD] is a major subtype of inflammatory bowel diseases [IBD] with increasing incidence and prevalence. Results of studies using available small and large animal models are often poorly translatable to patients, and few CD models show small intestinal pathology. Due to its similarities to humans, the pig has emerged as a highly suitable translational disease model, particularly for testing novel nutritional and technological interventions.

Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value).

This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value.