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ABSTRACTThe ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant S. Typhimurium (ST313 D23580) under different fluid shear conditions relevant to its transition from the intestinal tract to the bloodstream. We report that D23580 exhibited incremental changes in transcriptomic profiles that correlated with its pathogenic phenotypes in response to these progressive increases in fluid shear. This is the first demonstration that incremental changes in fluid shear forces alter stress responses and gene expression in any ST313 strain and offers mechanistic insight into how forces encountered by bacteria during infection might impact their disease-causing ability in unexpected ways.

Abstract Background Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. Methods The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into “no,” “occasional,” and “frequent” meal-related abdominal pain groups based on 0%, 10–40%, and ≥50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. Results Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. Conclusion Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.

Introduction: Disorders of gut‐brain interaction (DGBI) are symptom‐based disorders categorized by anatomic location but have high overlap and heterogeneity. Viewing DGBI symptoms on a spectrum (i.e. dimensionally) rather than categorically may better inform interventions to accommodate complex clinical presentations. We aimed to evaluate symptom networks to identify how DGBI symptoms interact. Methods: We used the Rome IV Diagnostic Questionnaire continuously/ordinally scored items collected from the Rome Foundation Global Epidemiology Study. We excluded participants who reported ≥1 organic/structural gastrointestinal disorder(s). We sought to (1) identify core symptoms in the DGBI symptom networks, (2) identify bridge pathways between Rome IV diagnostic categories (esophageal, bowel, gastroduodenal, anorectal), and (3) explore how symptoms group together into communities. Results: Of 54,127 adults, 20,229 met criteria for at least one DGBI (age mean = 42.2 ± 15.5; 57% female). General abdominal pain and epigastric pain were the core symptoms in the DGBI symptom network (i.e., had the strongest connections to other symptoms). Pain symptoms emerged as bridge pathways across existing DGBI diagnostic anatomic location (i.e., abdominal pain connected to chest pain, epigastric pain, rectal pain). Without a priori category definitions, exploratory network community analysis showed that symptoms grouped together into "pain," "gastroduodenal," and "constipation," rather than into groups by anatomic location. Conclusion: Our findings suggest pain symptoms are central and serve as a key connection to other symptoms, crosscutting anatomic location. Future longitudinal research is needed to test symptom network relations longitudinally and investigate whether targeting pain symptoms (rather than anatomic‐ or disorder‐specific symptoms) has clinical impact. [ABSTRACT FROM AUTHOR]

Background: Disorders of gut–brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world. Method s : We performed an ecological study utilizing peer‐reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI). Key Results: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = −0.57, 95% CI: −0.92, −0.22, p = 0.002) and happiness scores (β = −0.433 95% CI: 0.821, −0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = −0.50, 95% CI: −0.86, −0.13, p = 0.01) and happiness scores (β = −0.497, 95% CI: −0.863, −0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = −0.43, 95% CI: −0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = −0.40, 95% CI: −0.79, −0.014, p = 0.043) and happiness scores (β = −0.390, 95% CI: −0.778, −0.003, p = 0.049). Conclusions & Inferences: Utilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio‐cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world. [ABSTRACT FROM AUTHOR]

Background and Aims: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms. Methods: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych). Key Results: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2‐class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty‐two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%–97% for 2 clusters and 71–79% for 6 classes and 51%–63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non‐DGBI (range 97% with 2 clusters to 65% with 22 classes) groups. Conclusions & Inferences: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut‐brain interaction (DGBI). The Rome IV criteria are the gold standard for research when diagnosing DGBI. However, bothersomeness, or the degree to which symptoms are distressing or disruptive to a person's daily life, is a potential treatment‐seeking motivator that is not assessed by the Rome criteria. The Rome Foundation developed and published diagnostic criteria for clinical practice that include bothersomeness. We aimed to evaluate these constructs via patient focus groups to determine what prompts healthcare‐seeking as a means to assess its value in the Rome clinical criteria. Methods: Adults meeting Rome IV criteria for IBS, FD, or both participated in focus groups in Australia and the United States. Semi‐structured interview transcripts were analyzed using Template Thematic Analysis, with three a priori and other a posteriori themes refined iteratively through team discussion and consensus. Key Results: Participants confirmed the frequency and duration of symptoms was not sufficient to reflect illness experience. Four major themes emerged: (1) Bothersomeness should be included in assessments of IBS and FD; (2) Patients find many DGBI symptoms bothersome; (3) Bothersomeness traverses multiple domains of quality of life; (4) Patients may hesitate to seek medical advice due to past negative experiences. Conclusions and Inferences: These findings support the value of the Rome Clinical Criteria. They emphasize the importance of expanding assessments of patients with DGBI to include how bothersome they perceive symptoms to be, how much symptoms interfere with their daily life, and what may moderate their decisions to seek treatment. [ABSTRACT FROM AUTHOR]