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Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine that primarily affects older adults and presents with chronic diarrhea. The etiology is unknown and there are currently no FDA approved medications or biomarkers for treatment or monitoring of the disease. Emerging evidence have implicated the gut microbiome and metabolome disturbances in MC pathogenesis. We conduct a comprehensive analysis of gut microbial and metabolic changes in a cohort of 683 participants, including 131 patients with active MC, 159 with chronic diarrhea, and 393 age- and sex-matched controls without diarrhea. Stool microbiome and metabolome are profiled using whole-genome shotgun metagenomic sequencing and ultra-high performance liquid chromatography–mass spectrometry, respectively. Compared to controls, eight microbial species including pro-inflammatory oral-typical Veillonella dispar and Haemophilus parainfluenzae , and 11 species, including anti-inflammatory Blautia glucerasea and Bacteroides stercoris are enriched and depleted in MC, respectively. Pro-inflammatory metabolites, including lactosylceramides, ceramides, lysophospholipids, and lysoplasmalogens, are enriched in active MC. Multi-omics analyses reveal robust associations between microbial species, metabolic pathways, and metabolites, suggesting concordant disruptions in MC. Here, we show distinct shifts in gut microbiome and metabolome in MC that can inform the development of non-invasive biomarkers and novel therapeutics. Here, the authors identify distinct gut microbiome and metabolome signatures in microscopic colitis, a condition causing chronic diarrhea, highlighting pro-inflammatory species and metabolites as potential non-invasive biomarkers and therapeutic targets.

Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine and a common cause of chronic diarrhea in older adults. Here, we use single-cell RNA sequencing analysis of colonic mucosal tissue to build a cellular and molecular model for MC. Our results show that in MC, there is a substantial expansion of tissue CD8 +  T cells, likely arising from local expansion following T cell receptor engagement. Within the T cell compartment, MC is characterized by a shift in CD8 tissue-resident memory T cells towards a highly cytotoxic and inflammatory phenotype and expansion of CD4 +  T regulatory cells. These results provide insight into inflammatory cytokines shaping MC pathogenesis and highlight notable similarities and differences with other immune-mediated intestinal diseases, including a common upregulation of IL26 and an MC-specific upregulation of IL10 . These data help identify targets against enteric T cell subsets as an effective strategy for treatment of MC. Microscopic colitis is a chronic inflammatory disease of the large intestine. Here the authors use single-cell RNA transcriptomic profiling and tissue localization studies to characterise the colon immune cell populations in MC, showing expansion of CD8 T cells with diverse TCR clonotypes and expression of CD4 T reg cell signatures.

Background Colonic diverticulosis, the most common lesion found in routine colonoscopy, affects more than 50% of individuals aged ≥ 60 years. Emerging evidence suggest that dysbiosis of gut microbiota may play an important role in the pathophysiology of diverticular disease. However, specific changes in microbial species and metabolic functions in asymptomatic diverticulosis remain unknown. Methods In a cohort of US adults undergoing screening colonoscopy, we analyzed the gut microbiota using shotgun metagenomic sequencing. Demographic factors, lifestyle, and medication use were assessed using a baseline questionnaire administered prior to colonoscopy. Taxonomic structures and metabolic pathway abundances were determined using MetaPhlAn3 and HUMAnN3. We used multivariate association with linear models to identify microbial species and metabolic pathways that were significantly different between asymptomatic diverticulosis and controls, while adjusting for confounders selected a priori including age at colonoscopy, sex, body mass index (BMI), and dietary pattern. Results Among 684 individuals undergoing a screening colonoscopy, 284 (42%) had diverticulosis. Gut microbiome composition explained 1.9% variation in the disease status of asymptomatic diverticulosis. We observed no significant differences in the overall diversity of gut microbiome between asymptomatic diverticulosis and controls. However, microbial species Bifidobacterium pseudocatenulatum and Prevotella copri were significantly enriched in controls ( q value = 0.19 and 0.14, respectively), whereas Roseburia intestinalis , Dorea sp. CAG:317, and Clostridium sp. CAG: 299 were more abundant in those with diverticulosis ( q values = 0.17, 0.24, and 0.10, respectively). We observed that the relationship between BMI and diverticulosis appeared to be limited to carriers of Bifidobacterium pseudocatenulatum and Roseburia intestinalis ( P interaction  = 0.09). Conclusions Our study provides the first large-scale evidence supporting taxonomic and functional shifts of the gut microbiome in individuals with asymptomatic diverticulosis. The suggestive interaction between gut microbiota and BMI on prevalent diverticulosis deserves future investigations.

Background Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). Results Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (P trend  = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60–1.17) with five to seven servings per week and 0.62 (95% CI, 0.44–0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41–0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All P interaction  > 0.055). Conclusion In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

BackgroundMicroscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce.AimsTo compare clinical characteristics and treatment response by age at diagnosis.MethodsThis retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were ‘younger’ if age at diagnosis was ≤ 50 years and ‘older’ if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered ‘responders’ if they had remission or response and ‘non-responders’ if they had non-response or intolerance.ResultsWe included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m2, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07).ConclusionsThere are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.

Any pre-existing claims for breach of covenant (for example, rent aneare or dilapidations) will be presen'cd. However, if the reinstatement provision requires the landlord to sene a notice before the end of the term, the right to require the tenant to reinstate may be lost. In all cases, the safest course is to consider at an early stage whether alterations have been carried out and, if so, whether reinstatement is required.

Background: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). Results: Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (P trend =0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60-1.17) with five to seven servings per week and 0.62 (95% CI, 0.44-0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41-0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All P interaction >0.055). Conclusion: In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis. Key Words : Diverticulosis, Diet, Fruit and Vegetables, and Epidemiology

These principles were considered in the context of commercial leases for possibly the first time in Martin Retail Group Ltd v Crawley Borough Council [2014] EGILR 17, which concerned the unopposed renewal of a lease of a unit in a parade of shops in Crawley, West Sussex, owned by the local authority. The current lease permitted use as a newsagent but prohibited the sale of alcohol, groceries and convenience foods as part of a \"letting scheme\" covering the whole parade.

The landlord can refuse a new tenancy under section 30(l)(a) of the Act - \"where... the tenant has any obligations as respects the repair and maintenance... the tenant ought not to be granted a new tenancy in view of the state of repair of the holding, being a state resulting from the tenant's failure to comply with the said obligations\" (\"ground A\").

In PGF, the claimant was the landlord of commercial premises bringing a substantial claim for damages for dilapidations. The defendant denied the claim, relying on section 18 of the 1527 Act. The claimant twice sent the defendant reasoned proposals for mediation, but the defendant foiled to respond and no mediation took place.