Background/Aims: Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods: We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient’s stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results: We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4’s downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.

Background/Aims: Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods: We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient’s stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results: We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4’s downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.

OBJECTIVES: Season of birth, an exogenous indicator of early life environment, has been related to higher risk of adverse psychiatric outcomes but the findings for Alzheimer's disease (AD) have been inconsistent. We investigated whether the month or season of birth are associated with AD. METHODS: A nationwide nested case-control study including all community-dwellers with clinically verified AD diagnosed in 2005 to 2012 (n=70 719) and up to four age- sex- and region of residence-matched controls (n=282 862) residing in Finland. Associations between month and season of birth and AD were studied with conditional logistic regression. RESULTS: Month of birth was not associated with AD (p=0.09). No strong associations were observed with season (p=0.13), although in comparison to winter births (December-February) summer births (June-August) were associated with higher odds of AD (odds ratio, 1.03; 95% confidence interval, 1.00 to 1.05). However, the absolute difference in prevalence in winter births was only 0.5% (prevalence of those born in winter were 31.7% and 32.2% for cases and controls, respectively). CONCLUSIONS: Although our findings do not support the hypothesis that season of birth is related to AD/dementia risk, they do not invalidate the developmental origins of health and disease hypothesis in late-life cognition. It is possible that season does not adequately capture the early life circumstances, or that other (postnatal) risk factors such as lifestyle or socioeconomic factors overrule the impact of prenatal and perinatal factors.
Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease/*diagnosis/epidemiology ; Case-Control Studies ; Finland ; Humans ; Logistic Models ; Middle Aged ; Odds Ratio ; Risk Factors ; Seasons