The purpose is to analyze the prevalence of intestinal infection in patients with pneumonia in intensive care units (ICU) and the impact of intestinal infection on the prognosis of patients with pneumonia, so as to explore the bidirectional association between pneumonia and intestinal infection. The study aims to investigate the correlation between the occurrence of pneumonia and intestinal infection among patients in the ICU, utilizing the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, as well as the impact of intestinal infection on the prognosis of pneumonia patients. The enrolled patients were first divided into pneumonia group and non-pneumonia group, and the primary outcome was that patients developed intestinal infection. Multivariate logistic regression was used to elucidate the association between pneumonia and the prevalence of intestinal infection, and propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were used to validate our findings. We then divided patients with pneumonia into two groups according to whether they were complicated by intestinal infection, and analyzed the effect of intestinal infection on 28-day mortality, length of ICU stay, and length of hospital stay in patients with pneumonia. This study included 50,920 patients, of which 7493 were diagnosed with pneumonia. Compared with non-pneumonia patients, the incidence of intestinal infection in pneumonia patients was significantly increased [OR 1.58 (95% CI 1.34-1.85; P < 0.001)]. Cox proportional hazards regression model showed no significant effect of co-infection on 28-day mortality in patients with pneumonia (P = 0.223). Patients in the intestinal infection group exhibited a longer length stay in ICU and hospital than those without intestinal infection (P < 0.001). In the ICU, patients with pneumonia were more likely linked to intestinal infection. In addition, the presence of concurrent intestinal infections can prolong both ICU and hospital stays for pneumonia patients.

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms.

Examining the interplay between intestinal pathogens and the gut microbiota is crucial to fully comprehend the pathogenic role of enteropathogens and their broader impact on human health. Valid alternatives to human studies have been introduced in laboratory practice to evaluate the effects of infectious agents on the gut microbiota, thereby exploring their translational implications in intestinal functionality and overall health. Different animal species are currently used as valuable models for intestinal infections. In addition, considering the recent advances in bioengineering, futuristic in vitro models resembling the intestinal environment are also available for this purpose. In this review, the impact of the main human enteropathogens (i.e., Clostridioides difficile, Campylobacter jejuni, diarrheagenic Escherichia coli, non-typhoidal Salmonella enterica, Shigella flexneri and Shigella sonnei, Vibrio cholerae, and Bacillus cereus) on intestinal microbial communities is summarized, with specific emphasis on results derived from investigations employing animal and in vitro models.

Prolonged diarrhoea (ProD) refers to acute-onset diarrhoea that persists for longer than 1 week. As the aetiology, risk factors and management are poorly defined, we prospectively enrolled children hospitalised in a high-income setting to assess these outcomes and investigate the potential role of gut microbiota.
All children aged 30 days to 14 years admitted for acute-onset diarrhoea lasting 7-14 days were included. Children consecutively admitted in the same period for acute diarrhoea (AD) served as controls. High-throughput sequencing of 16S rRNA gene amplicons was used to analyse stool samples from a subset of patients and healthy controls.
Sixty-eight with ProD and 104 with AD were enrolled. Intestinal infections were the main aetiology of diarrhoea in both groups (ProD 92.9% vs. AD 97.8%). ProD children showed a higher prevalence of bacterial infections compared to AD (30.8% vs. 8.9%, p = 0.024). Neither age, host-related factors, nor microbiome alterations were specifically linked to ProD. However, ProD children had a more severe initial clinical presentation than AD.
ProD is often the result of an unusually severe intestinal infection that runs a course longer than expected but generally resolves without further problems. No specific management or therapies should be undertaken in most cases.

Streptococcus dysgalactiae subsp. equisimillis (SDSE) is classified as a group G streptococcus (GGS). In systemic SDSE infection, septic shock is easily induced and has a high mortality of 44%. The case was a 78-year-old man presented with fever and chills of 20 hours duration. He was in shock at the presentation and developed melena on day nine. CT images showed bowel wall thickening with emphysema and bedside colonoscopy showed active bleeding in the descending colon and rectum. Blood cultures were positive for Streptococcus dysgalactiae and a diagnosis of streptococcal toxic shock syndrome (STSS) due to SDSE was made. Urgent Hartmann procedure with laparotomy for removal of descending and rectal colon was performed to relieve his shock status. His shock status was reversed after surgery. Surgical specimens confirmed the presence of SDSE on the intestinal mucosa. This is the first case of STSS due to SDSE infection of the intestinal wall. Resection of infected tissue in the setting of multiple organ dysfunction syndrome and necrotizing enterocolitis is indicated in such cases.

Shigella spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates\' protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon Shigella oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (Shigella sonnei, Shigella flexneri 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased Shigella penetration into the colon epithelium layer in a Gulo-/- mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both Shigella infection strategies and immune responses to Shigella infection.

Salmonella Reading is a rare serotype of Salmonella enterica and is associated with sporadic cases and rare outbreaks worldwide. This article describes a rare case of generalized S. Reading infection imported from Indonesia to Moscow, Russia. A 37-year-old man was admitted to the hospital with fever, weakness, and headache after returning from Indonesia. During his stay in Indonesia, he developed symptoms of a gastrointestinal infection, which resolved there. However, upon return to Moscow, his condition worsened due to high fever, and he was diagnosed with a generalized salmonellosis caused by S. Reading (positive blood and stool culture). This case highlights the importance of differential diagnosis in patients with fever. The health risks associated with traveling to exotic countries and the importance of preventive measures are emphasized. This is the first published case of S. Reading in Eastern Europe.

Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. To our knowledge, our study first identified TLR7 as a critical factor that contributes to the immunopathology of CDI, suggesting that targeting TLR7 might serve as a potential treatment for CDI.

Antibiotic colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin-resistant bacteria via a checkerboard assay. For the co-delivery of curcumin and colistin, negatively charged poly(ethylene glycol)-functionalized liposomes encapsulating both drugs (Lipo-cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo-cc against colistin-resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo-cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo-cc does not exhibit any toxicity. The therapeutic efficacy of Lipo-cc is further demonstrated in an intestinal bacterial infection model induced with colistin-resistant Escherichia coli. Lipo-cc reduces the bacterial burden with over 6-log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo-cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo-cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin-resistant bacterial infections.

UNASSIGNED: The gut microbiome may play an important role in the etiology and progression of colon cancer. The present hypothesis-testing study compared the colon cancer incidence rate among adults diagnosed with intestinal Clostridioides (formerly Clostridium) difficile (Cdiff) (the Cdiff cohort) to adults not diagnosed with intestinal Cdiff infection (the non-Cdiff cohort).
UNASSIGNED: De-identified eligibility and claim healthcare records within the Independent Healthcare Research Database (IHRD) from a longitudinal cohort of adults (the overall cohort) enrolled in the Florida Medicaid system between 1990 through 2012 were examined. Adults with ≥ 8 outpatient office visits over 8 years of continuous eligibility were examined. There were 964 adults in the Cdiff cohort and 292,136 adults in the non-Cdiff cohort. Frequency and Cox proportional hazards models were utilized.
UNASSIGNED: Colon cancer incidence rate in the non-Cdiff cohort remained relatively uniform over the entire study period, whereas a marked increase was observed in the Cdiff cohort within the first 4 years of a Cdiff diagnosis. Colon cancer incidence was significantly increased (about 2.7-fold) in the Cdiff cohort (3.11 per 1,000 person-years) compared to the non-Cdiff cohort (1.16 per 1,000 person-years). Adjustments for gender, age, residency, birthdate, colonoscopy screening, family history of cancer, and personal history of tobacco abuse, alcohol abuse/dependence, drug abuse/dependence, and overweight/obesity, as well as consideration of diagnostic status for ulcerative and infection colitis, immunodeficiency, and personal history of cancer did not significantly change the observed results.
UNASSIGNED: This is the first epidemiological study associating Cdiff with an increased risk for colon cancer. Future studies should further evaluate this relationship.