Salmonella not only causes acute infections, but can also cause patients to become chronic “asymptomatic” carriers. Salmonella has been verified as a pathogenic factor that contributes to chronic inflammation and carcinogenesis. This review summarizes the acute and chronic Salmonella infection and describes the current research progress of Salmonella infection contributing to inflammatory bowel disease and cancer. Furthermore, this review explores the underlying biological mechanism of the host signaling pathways manipulated by Salmonella effector molecules. Using experimental animal models, researchers have shown that Salmonella infection is related to host biological processes, such as host cell transformation, stem cell maintenance, and changes of the gut microbiota (dysbiosis). Finally, this review discusses the current challenges and future directions in studying Salmonella infection and its association with human diseases.

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 2019 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19 patients. This article focuses on gastrointestinal symptoms and pathophysiology in COVID-19 disease. Evidence suggests that the gastrointestinal tract could be a viral target for SARS-CoV-2 infection. Not only is the SARS-CoV-2 receptor ACE2 highly expressed in the GI tract and is associated with digestive symptoms, but bleeding and inflammation are observed in the intestine of COVID-19 patients. We further systemically summarize the correlation between COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The potential oral-fecal transmission of COVID-19 was supported by viral RNA and live virus detection in the feces of COVID-19 patients. Additionally, the viral balance in the GI tract could be disordered during SARS-CoV-2 infection which could further impact the homeostasis of the gut microbial flora. Finally, we discuss the clinical and ongoing trials of treatments/therapies, including antiviral drugs, plasma transfusion and immunoglobulins, and diet supplementations for COVID-19. By reviewing the pathogenesis of SARS-CoV-2 virus, and understanding the correlation among COVID-19, inflammation, intestinal microbiota, and lung microbiota, we provide perspective in prevention and control, as well as diagnosis and treatment of the COVID-19 disease.

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as the critically ignored “organ,” the intestinal microbiome greatly impacts physiological health, not only in gastrointestinal diseases but also in disorders beyond the gut. However, the correlation between S. aureus infection and intestinal microbial homeostasis is largely unknown. Here, we summarized the recent progress in understanding S. aureus infections and their interactions with the microbiome in the intestine. These summarizations will help us understand the mechanisms behind these infections and crosstalk and the challenges we are facing now, which could contribute to preventing S. aureus infections, effective treatment investigation, and vaccine development.

The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDR^ΔIEC) mice with dysbiosis. We reported that VDR^ΔIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDR^ΔIEC mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.

Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1^ΔIEC) and Paneth cell (PC; Axin1^ΔPC) to compare with control (Axin1^LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1^ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vivo. Axin1^ΔIEC and Axin1^ΔPC mice became more susceptible to DSS-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1^Loxp mice. However, the intestinal proliferative cells in Axin1^ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1^ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

Background/Objective: Tight junctions (TJs) are essential for barrier integrity, inflammation, and cancer. The TJ protein Claudin-5 in the epithelia forms paracellular barriers and pores for permeability. Vitamin D and the vitamin D receptor (VDR) play important roles in various cancers. Although VDR and Claudin-5 are all involved in colorectal cancer (CRC), it remains unclear if they are closely related or function independently. Design: Using the human CRC database, we explored the correlation between VDR and Claudin-5. We then investigated the VDR regulation of Claudin-5 using VDR knockout (VDR ^-/- ) and intestinal epithelial VDR knockout mice (VDR ^ΔIEC ) with chemical-induced colon cancer and an epithelial VDR overexpression model. Human samples, organoids, and intestinal epithelial cells were used to determine the underlying mechanisms. Results: In human colon cancer, colonic VDR expression was low and was significantly correlated with a reduction of Claudin-5 mRNA and protein. In the colon of VDR ^-/- and VDR ^ΔIEC mice, deletion of VDR led to lower protein and mRNA levels of Claudin-5. Intestine permeability was increased in the AOM-DSS-induced VDR ^-/- colon cancer model. Lack of VDR and a reduction of Claudin-5 are associated with an increased number of tumors in the VDR ^-/- and VDR ^ΔIEC mice. Furthermore, gain and loss of function studies have identified CLDN-5 as a downstream target of the VDR signaling pathway. Epithelial VDR overexpression protected against the loss of Claudin 5 in response to intestinal inflammation Conclusion: This study advances the understanding of how VDR regulates intestinal barrier functions in tumorigenesis as a biomarker and potential treatment. A short summary: What is already known about this subject? Tight junction structures are essential for intestinal barrier integrity, inflammation, and cancer. Vitamin D deficiency and the vitamin D receptor (VDR) play important roles in the development of colon cancer. What are the new findings? Our study is the first to link barrier function, a specific tight junction protein, and genetic susceptibility through intestinal epithelial VDR in human colorectal cancer. Our study fills an existing gap by characterizing the mechanism of intestinal epithelial VDR in regulating barrier functions through alterations in TJs in tumorigenesis. VDR is important for the maintenance of the physiological level of the TJ protein Claudin-5 in the colon. The CLDN-5 gene is a downstream target of the VDR signaling pathway. Lack of VDR led to a reduction of Claudin-5 in tumors, whereas enhancing VDR increased Claudin-5 to protect the intestinal epithelial cells from tumorigenesis. We report fecal VDR reduction in a colon cancer model. This introduces the possibility for the identification of new biomarkers and therapeutic targets to restore VDR-dependent functions in CRC. How might it impact on clinical practice in the foreseeable future Diagnosis of CRC considering VDR status Barrier: direct, indirect biomarkers Intestinal barriers in cancer prevention and treatment Barrier function and VDR are not only essential for the maintenance of intestinal homeostasis, but they are also critical for the development of chronic mucosal inflammation and cancer. This knowledge can be immediately used to develop intestinal VDR and Claudin-5 as clinical biomarkers for identifying patients who may benefit from currently available interventions and could also be used for the eventual development of novel strategies for the prevention and treatment of human CRC.