Fungal xenosiderophores from mycobiota and diet promote Salmonella colonization of the inflamed gut

The fungal gut microbiota (mycobiota) has been implicated in diseases that disturb gut homeostasis. However, little is known about functional relationships between bacteria and fungi in the gut during infectious colitis. We investigated the role of fungal metabolites during infection with the intestinal pathogen Salmonella enterica serovar Typhimurium. We found that in the gut lumen, both the mycobiota and fungi present in the diet can be a source of siderophores, small molecules that scavenge iron from the host. The ability to use fungal siderophores, such as ferrichrome and coprogen, conferred a competitive growth advantage to Salmonella strains expressing the fungal siderophore receptors FhuA or FhuE in vitro and in a mouse model. Our study highlights the role of inter-kingdom cross-feeding between fungi and Salmonella, and elucidates a new function for the gut mycobiota, revealing the importance of these under-studied members of the gut ecosystem during bacterial infection.

Dietary Interventions Ameliorate Infectious Colitis by Restoring the Microbiome and Promoting Stem Cell Proliferation in Mice

Decreases in short-chain-fatty-acids (SCFAs) are linked to inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious colitis, treatment with Pectin and Tributyrin diets reduced the severity of colitis by restoring Firmicutes and Bacteroidetes and by increasing mucus production. RNA-seq in young adult mouse colon (YAMC) cells identified higher expression of Lgr4, Lgr6, DCLK1, Muc2, and SIGGIR after Butyrate treatment. Lineage tracing in CR-infected Lgr5-EGFP-IRES-CreERT2/ROSA26-LacZ (Lgr5-R) mice also revealed an expansion of LacZ-labeled Lgr5(+) stem cells in the colons of both Pectin and Tributyrin-treated mice compared to control. Interestingly, gut microbiota was required for Pectin but not Tributyrin-induced Lgr5(+) stem cell expansion. YAMC cells treated with sodium butyrate exhibited increased Lgr5 promoter reporter activity due to direct Butyrate binding with Lgr5 at −4.0 Kcal/mol, leading to thermal stabilization. Upon ChIP-seq, H3K4me3 increased near Lgr5 transcription start site that contained the consensus binding motif for a transcriptional activator of Lgr5 (SPIB). Thus, a multitude of effects on gut microbiome, differential gene expression, and/or expansion of Lgr5(+) stem cells seem to underlie amelioration of colitis following dietary intervention.

Atypical Presentation of Colonic Diverticular Disease

Hematochezia or passage of fresh blood per rectum is a relatively common finding in medical practice which mostly indicates lower gastrointestinal bleeding. The causes for lower gastrointestinal bleeding include diverticular disease, vascular ectasia, ischemic, inflammatory or infectious colitis, colonic neoplasia, hemorrhoids, anal fissures and small bowel lesions (Crohn’s disease, Vascularectasia, Meckel’s diverticulum).If a patient comes with severe hematochezia, the first and foremost task is to stabilize the patient and then find out the source of bleeding as soon as possible. Elderly patients presenting with severe hematochezia, is most likely due to colorectal malignancy but benign causes like colonic diverticulosis can also present as life threatening bleeding in rare occasions. Here we report a case of 70-years-old male patient presenting with severe painless hematochezia leading to severe anemia due to diverticulosis. Bangladesh J Medicine July 2022; 33(1) : 94-98

Causes and Management of Lower Gastro-Intestinal Bleeding

Gastrointestinal (GI) bleeding from the colon is a communal reason for hospitalization and is being more frequent in older patients. Gastrointestinal bleeding is known as any bleeding that takes place in the GIT from mouth to anus. Lower GI bleeding is defined as bleeding distal to the ligament of Treitz. Lower GI bleed is typically presented as hematochezia which is the passing of bright red blood clots or burgundy stools through the rectum. The causes of lower GI bleeding are changing over the past several decades from diverticulosis (which is the protrusion of the colon wall at the site of penetrating vessels), infectious colitis, ischemic colitis, angiodysplasia, inflammatory bowel disease, colon cancer, hemorrhoids, anal fissures, rectal varices, dieulafoy lesion, radiation-induced damage following cancer treatment to post-surgical. Management of lower GI bleeding is done through assessing the severity of symptoms and the condition of the overall case.

Experience of X-ray control of the effectiveness of antibiotic therapy for post-infectious colitis

We observed 50 patients aged 30 to 60 years. Colitis after dysentery - 26, after toxicoinfections - 5, colitis of mixed etiology - 14, alimentary etiology - 2 and unclear - 3 people. 28 had relapses, and 22 had a monotonous course. From concomitant diseases, anacid, normocidal and hyperacid gastritis prevailed. Angiocholecystitis and mesenchymal hepatitis were diagnosed in 29 patients.

Interleukin-4 Programmed Macrophages Suppress Colitis and Do Not Enhance Infectious-Colitis, Inflammation-Associated Colon Cancer or Airway Hypersensitivity

The murine interleukin-4 treated macrophage (MIL4) exerts anti-inflammatory and pro-healing effects and has been shown to reduce the severity of chemical-induced colitis. Positing M(IL4) transfer as an anti-inflammatory therapy, the possibility of side-effects must be considered. Consequently, bone marrow-derived M(IL4)s were administered via intraperitoneal injection to mice concomitant with Citrobacter rodentium infection (infections colitis), azoxymethane/dextran sodium sulphate (AOM/DSS) treatment [a model of colorectal cancer (CRC)], or ovalbumin sensitization (airway inflammation). The impact of M(IL4) treatment on C. rodentium infectivity, colon histopathology, tumor number and size and tissue-specific inflammation was examined in these models. The anti-colitic effect of the M(IL4)s were confirmed in the di-nitrobenzene sulphonic acid model of colitis and the lumen-to-blood movement of 4kDa FITC-dextran and bacterial translocation to the spleen and liver was also improved by M(IL4) treatment. Analysis of the other models of disease, that represent comorbidities that can occur in human inflammatory bowel disease (IBD), revealed that M(IL4) treatment did not exaggerate the severity of any of the conditions. Rather, there was reduction in the size (but not number) of polyps in the colon of AOM/DSS-mice and reduced infectivity and inflammation in C. rodentium-infected mice in M(IL4)-treated mice. Thus, while any new therapy can have unforeseen side effects, our data confirm and extend the anti-colitic capacity of murine M(IL4)s and indicate that systemic delivery of one million M(IL4)s did not exaggerate disease in models of colonic or airways inflammation or colonic tumorigenesis.