The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt\'s functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Entomopathogenic fungi may interact with insects\' symbiotic bacteria during infection. We hypothesized that topical infection with Beauveria bassiana may alter the microbiota of the Colorado potato beetle (CPB) and that these modifications may alter the course of mycoses. We used a model with two concentrations of conidia: (1) high concentration that causes rapid (acute) pathogenesis with fast mortality followed by bacterial decomposition of insects; (2) lower concentration that leads to prolonged pathogenesis ending in conidiation on cadavers. The fungal infections increased loads of enterobacteria and bacilli on the cuticle surface and in hemolymph and midgut, and the greatest increase was detected during the acute mycosis. By contrast, stronger activation of IMD and JAK-STAT signaling pathways in integuments and fat body was observed during the prolonged mycosis. Relatively stable (nonpathogenic) conditions remained in the midgut during both scenarios of mycosis with slight changes in bacterial communities, the absence of mesh and stat expression, a decrease in reactive oxygen species production, and slight induction of Toll and IMD pathways. Oral administration of antibiotic and predominant CPB bacteria (Enterobacteriaceae, Lactococcus, Pseudomonas) led to minor and mainly antagonistic effects in survival of larvae infected with B. bassiana. We believe that prolonged mycosis is necessary for successful development of the fungus because such pathogenesis allows the host to activate antibacterial reactions. Conversely, after infection with high concentrations of the fungus, the host\'s resources are insufficient to fully activate antibacterial defenses, and this situation makes successful development of the fungus impossible.

Clostridioides difficile infection (CDI) poses a significant health threat due to high recurrence rates. Antimicrobial agents are commonly used to manage CDI-related diarrhoea; however, by aggravating intestinal dysbiosis, antibiotics enable C. difficile spores germination and production of toxins, the main virulence factors. Therefore, the binding of exotoxins using adsorbents represents an attractive alternative medication for the prevention and treatment of relapses. In this study, we provided evidence that the natural insoluble polysaccharides, named ABR119, extracted by plant cell cultures, effectively trap C. difficile toxins. In our experiments, ABR119 exhibited no cytotoxicity in vitro and was safely administered in vivo. In the animal model of C. difficile-associated colitis, ABR119 (50 mg/kg body weight) significantly reduced the colonic myeloperoxidase activity and severity of inflammation, preventing body weight loss. These effects were not evident when we treated animals with wheat bran polysaccharides. We did not detect bacterial killing effects of ABR119 against C. difficile nor against bacterial species of the normal gut microbiota. Moreover, ABR119 did not interfere in vitro with the antimicrobial activities of most clinically used antibiotics. In summary, ABR119 holds promise for treating and preventing C. difficile colitis by trapping the bacterial toxins, warranting further studies to assess the ABR119 potential in human infections caused by C. difficile.

Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut-/-) were generated by crossing Vil-Cre and floxed neprilysin (NEPfl/fl) mice. Neprilysin activity was almost abolished throughout the gut in NEPGut-/- mice, and was similar in plasma, pancreas and kidney in NEPGut-/- vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut-/- displayed lower fasting plasma glucose levels, improved glucose tolerance and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in high-fat-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction.

UNASSIGNED: The administration of antibiotics can expose the digestive microbiota of humans and animals to sub-inhibitory concentrations, potentially favouring the selection of resistant bacteria. The minimal selective concentration (MSC) is a key indicator to understand this process. The MSC is defined as the lowest concentration of an antibiotic that promotes the growth of a resistant strain over a susceptible isogenic strain. It represents the lower limit of the sub-minimal inhibitory concentration (MIC) selective window, where resistant mutants can be selected. Previous studies focused on determining the MSC under standard culture conditions, whereas our research aimed to determine the MSC in a model that approximates in vivo conditions.
UNASSIGNED: We investigated the MSC of oxytetracycline (OTC) in Mueller-Hinton broth (MHB) and sterilised intestinal contents (SIC) from the jejunum, caecum and rectum (faeces) of pigs, using two isogenic strains of Escherichia coli (one susceptible and one resistant to OTC). Additionally, the MIC of OTC against the susceptible strain was determined to assess the upper limit of the sub-MIC selective window.
UNASSIGNED: Our study took a novel approach, and the results indicated that MIC and MSC values were lower in MHB than in SIC. In the latter, these values varied depending on the intestinal segment, with distal compartments exhibiting higher MIC and MSC values. Moreover, the sub-MIC selective window of OTC in SIC narrowed from the jejunum to the rectum, with a significantly closer MSC to MIC in faecal SIC.
UNASSIGNED: The results suggest that OTC binds to digestive contents, reducing the fraction of free OTC. However, binding alone does not fully explain our results, and interactions between bacteria and intestinal contents may play a role. Furthermore, our findings provide initial estimates of low concentrations facilitating resistance selection in the gut. Finally, this research enhances the understanding of antimicrobial resistance selection, emphasising the intricate interplay between antibiotics and intestinal content composition in assessing the risk of resistance development in the gut.

The immune system of bony fish closely resembles that of mammals, comprising both specific (adaptive) and non-specific (innate) components. Notably, the mucosa-associated lymphoid tissue (MALT) serves as the first line of defense within the non-specific immune system, playing a critical role in protecting these aquatic organisms against invading pathogens. MALT encompasses a network of immune cells strategically distributed throughout the gills and intestines, forming an integral part of the mucosal barrier that interfaces directly with the surrounding aquatic environment. Spring Viremia of Carp Virus（SVCV）, a highly pathogenic agent causing substantial harm to common carp populations, has been designated as a Class 2 animal disease by the Ministry of Agriculture and Rural Affairs of China. Utilizing a comprehensive array of research techniques, including Hematoxylin and Eosin (HE)、Alcian Blue Periodic Acid-Schiff (AB-PAS)、transcriptome analysis for global gene expression profiling and Reverse Transcription-Polymerase Chain Reaction (RT-qPCR), this study uncovered several key findings: SVCV is capable of compromising the mucosal architecture in the gill and intestinal tissues of carp, and stimulate the proliferation of mucous cells both in gill and intestinal tissues. Critically, the study revealed that SVCV\'s invasion elicits a robust response from the carp\'s mucosal immune system, demonstrating the organism\'s capacity to resist SVCV invasion despite the challenges posed by the pathogen.

The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121, consisting of probiotic microbes and prebiotic fibers was designed for the clinical dietary management of rheumatoid arthritis. A 28-day repeated administration study was performed to evaluate the oral toxicity of SBD121 in male and female rats (age/weight at study start: 60 days/ 156-264 grams) administered levels of 0, 4.96 x 1010, 2.48 x 1011, or 4.96 x 1011 colony forming units (CFU)/kg-bw. No treatment related changes in ophthalmological effects, mortality, morbidity, general health and clinical observations, urinalysis, hematology, serum chemistry, absolute or relative organ weights, gross necropsy, or histopathology. A significant decrease in body weight was reported in females in the low and high-concentration groups, which corresponded in part with a significant decrease in food consumption. Results of the functional observation battery indicated front grip strength was significantly greater in the high-concentration males compared to the controls; however, this effect was not considered adverse. Based on these findings, the administration of the Medical Food SBD121 to male and female rats has a no-observable adverse effect level (NOAEL) at the highest level tested of 4.96 x 1011 CFU/kg-bw.

UNASSIGNED: Eosinophilic esophagitis (EoE) is a chronic inflammatory, disabling disorder characterized by prominent eosinophilic inflammation of the esophagus, leading to troublesome symptoms including dysphagia and food impaction. The natural history of EoE is poorly known, but it may lead to esophageal strictures. The therapeutic armamentarium is expected to grow in the near future, especially due to the availability of novel biological therapies targeting crucial inflammatory pathways of EoE.
UNASSIGNED: In this review, we discuss the main clinical features and natural history of EoE, focusing on the current therapeutic strategies, as well as past and current trials investigating biologics for its treatment.
UNASSIGNED: Dupilumab has been the first approved biologic drug for the treatment of EoE; long-term studies assessing how it could change the natural history of EoE are awaited. Novel biological drugs or other molecules are currently under study and could change the current treatment algorithms in the near future. Proper drug positioning and long term \'exit strategies\' are yet to be defined.

Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single-, two- and three-cell culture systems to demonstrate the transmigration of Bacteroides thetaiotaomicron derived BEVs (Bt-BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells. Bt-BEVs were shown to traffic to the CNS in vivo after intravenous administration to mice, and in multi-cell in vitro culture systems to transmigrate across gut epithelial and BBB endothelial cell barriers, where they were acquired by both microglia and immature neuronal cells. No significant activation/inflammatory effects were induced in non-differentiated neurons, in contrast to that observed in microglia cells, although this was notably less than that induced by lipopolysaccharide (LPS). Overall, our findings provide evidence for transmigration of Bt-BEVs across gut-epithelial and BBB endothelial cell barriers in vivo and in vitro, and their downstream responses in neural cells. This study sheds light onto how commensal bacteria-derived BEV transport across the gut-brain axis and can be exploited for the development of targeted drug delivery.

[This corrects the article DOI: 10.3389/fnut.2022.1024722.].