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Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of proinflammatory cytokines IL-18 and IL-1a, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. CONCLUSIONS: P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome’s capability as a therapeutic avenue against COVID-19. Lay summary It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.

Background Elderly-onset inflammatory bowel disease (IBD), defined as age ≥60 at diagnosis, is increasing worldwide. We aimed to compare clinical characteristics and natural history of elderly-onset IBD patients to adult-onset IBD patients. Methods Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features and outcomes of elderly-onset IBD patients were compared to adult-onset IBD patients. Results A total of 2413 patients were identified, of whom 270 (11.2%) had elderly-onset IBD. Median follow-up duration was 111 months (Interquartile range [IQR]: 68-165 months). Ratio of ulcerative colitis (UC): Crohn’s disease (CD) was higher in elderly-onset IBD than adult-onset IBD patients (3.82:1 vs. 1.39:1; p&0.001). Elderly-onset CD had less perianal involvement (5.4% vs. 25.4%; p&.001) than adult-onset. Elderly-onset IBD patients had significantly lower cumulative use of immunomodulators (p=0.001) and biologics (p=0.04). Elderly-onset IBD was associated with higher risks of cytomegalovirus colitis (Odds ratio [OR]: 3.07; 95% Confidence Interval (CI) 1.92-4.89; p&0.001); herpes zoster (OR: 2.42; 95% CI: 1.22-4.80; p=0.12) and all cancer development (Hazard ratio: 2.97; 95% CI: 1.84-4.79; p&0.001). They also had increased number of overall hospitalization (OR: 1.14; 95% CI 1.09-1.20; p&0.001), infections-related hospitalization (OR: 1.87; 95% CI 1.47-2.38; p&0.001) and IBD-related hospitalization (OR: 1.09; 95% CI: 1.04- 1.15; p=0.001) compared to adult-onset IBD. Conclusion Elderly-onset IBD patients were associated with increased risk of infections, cancer development and increased infections- and IBD-related hospitalizations. Specific therapeutic strategies to target this special population is needed.