Intestinal biofilms: pathophysiological relevance, host defense, and therapeutic opportunities.

SUMMARYThe human intestinal tract harbors a profound variety of microorganisms that live in symbiosis with the host and each other. It is a complex and highly dynamic environment whose homeostasis directly relates to human health. Dysbiosis of the gut microbiota and polymicrobial biofilms have been associated with gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel diseases, and colorectal cancers. This review covers the molecular composition and organization of intestinal biofilms, mechanistic aspects of biofilm signaling networks for bacterial communication and behavior, and synergistic effects in polymicrobial biofilms. It further describes the clinical relevance and diseases associated with gut biofilms, the role of biofilms in antimicrobial resistance, and the intestinal host defense system and therapeutic strategies counteracting biofilms. Taken together, this review summarizes the latest knowledge and research on intestinal biofilms and their role in gut disorders and provides directions toward the development of biofilm-specific treatments.

Wright's Hierarchical F-Statistics.

This perspective article offers a meditation on FST and other quantities developed by Sewall Wright to describe the population structure, defined as any departure from reproduction through random union of gametes. Concepts related to the F-statistics draw from studies of the partitioning of variation, identity coefficients, and diversity measures. Relationships between the first two approaches have recently been clarified and unified. This essay addresses the third pillar of the discussion: Nei's GST and related measures. A hierarchy of probabilities of identity-by-state provides a description of the relationships among levels of a structured population with respect to genetic diversity. Explicit expressions for the identity-by-state probabilities are determined for models of structured populations undergoing regular inbreeding and recurrent mutation. Levels of genetic diversity within and between subpopulations reflect mutation as well as migration. Accordingly, indices of the population structure are inherently locus-specific, contrary to the intentions of Wright. Some implications of this locus-specificity are explored.

Gastrointestinal Biofilms: Endoscopic Detection, Disease Relevance, and Therapeutic Strategies.

Gastrointestinal biofilms are matrix-enclosed, highly heterogenic and spatially organized polymicrobial communities that can cover large areas in the gastrointestinal tract. Gut microbiota dysbiosis, mucus disruption, and epithelial invasion are associated with pathogenic biofilms that have been linked to gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel diseases, gastric cancer, and colorectal cancer. Intestinal biofilms are highly prevalent in ulcerative colitis and irritable bowel syndrome patients, and most endoscopists will have observed such biofilms during colonoscopy, maybe without appreciating their biological and clinical importance. Gut biofilms have a protective extracellular matrix that renders them challenging to treat, and effective therapies are yet to be developed. This review covers gastrointestinal biofilm formation, growth, appearance and detection, biofilm architecture and signalling, human host defence mechanisms, disease and clinical relevance of biofilms, therapeutic approaches, and future perspectives. Critical knowledge gaps and open research questions regarding the biofilm's exact pathophysiological relevance and key hurdles in translating therapeutic advances into the clinic are discussed. Taken together, this review summarizes the status quo in gut biofilm research and provides perspectives and guidance for future research and therapeutic strategies.

Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.

Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various biological processes, including the regulation of neurotransmitters, immune responses, cancer development, metabolism, and inflammation. This review encompasses key research studies related to the kynurenine pathway in the context of headache, neuropathic pain, gastrointestinal disorders, fibromyalgia, chronic fatigue syndrome, and MDD. Various metabolites produced in the kynurenine pathway, such as kynurenic acid and quinolinic acid, exhibit neuroprotective and neurotoxic effects, respectively. Recent studies have highlighted the significant involvement of kynurenine and its metabolites in the pathophysiology of pain. Moreover, pharmacological interventions targeting the regulation of the kynurenine pathway have shown therapeutic promise in pain management. Understanding the underlying mechanisms of this pathway presents an opportunity for developing personalized, innovative, and non-opioid approaches to pain treatment. Therefore, this narrative review explores the role of the kynurenine pathway in various chronic pain disorders and its association with depression and chronic pain.

Exploring the clinical significance of miR-148 expression variations in distinct subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) belongs to chronic functional gastrointestinal diseases featured by abdominal pain and changes in bowel habits. This study aimed to investigate the clinical significance of serum miR-148 expression in different subtypes of IBS. We enrolled 86 IBS patients and 55 healthy controls. miR-148 expression levels were assessed in IBS patients classified into IBS-constipation (IBS-C), IBS-diarrhea (IBS-D), and IBS-mixed stool pattern (IBS-M) subtypes. Receiver-operating characteristic (ROC) curves were employed to evaluate the diagnostic potential of miR-148 in distinguishing among IBS subtypes. Additionally, we analyzed the correlation between miR-148 expression and clinical characteristics, including IBS symptom severity. miR-148 expression was highest in IBS-D (diarrhea) group, followed by IBS-M and IBS-C. With the exception of the IBS-C group, miR-148 expression was elevated in IBS patients compared to controls. ROC curve analysis demonstrated that serum miR-148 exhibited higher diagnostic accuracy for discriminating IBS-C and IBS-D than IBS-M. Correlation analysis revealed a positive relationship between serum miR-148 relative expression and IBS symptom severity system scores. Univariate logistic analysis indicated a positive association between miR-148 expression and IBS-D and a negative correlation with IBS-C. miR-148 expression exhibits differential patterns among IBS subtypes and holds a potential to distinguish IBS-C and IBS-D. Furthermore, miR-148 expression correlates with the severity of IBS symptoms.

Nanopatterning Induced Si Doping in Amorphous Ga2O3 for Enhanced Electrical Properties and Ultra-Fast Photodetection.

Ga2O3 has emerged as a promising material for the wide-bandgap industry aiming at devices beyond the limits of conventional silicon. Amorphous Ga2O3 is widely being used for flexible electronics, but suffers from very high resistivity. Conventional methods of doping like ion implantation require high temperatures post-processing, thereby limiting their use. Herein, an unconventional method of doping Ga2O3 films with Si, thereby enhancing its electrical properties, is reported. Ion-beam sputtering (500 eV Ar+) is utilized to nanopattern SiO2-coated Si substrate leaving the topmost part rich in elemental Si. This helps in enhancing the carrier conduction by increasing n-type doping of the subsequently coated 5 nm amorphous Ga2O3 films, corroborated by room-temperature resistivity measurement and valence band spectra, respectively, while the nanopatterns formed help in better light management. Finally, as proof of concept, metal-semiconductor-metal (MSM) photoconductor devices fabricated on doped, rippled films show superior properties with responsivity increasing from 6 to 433 mA W-1 while having fast detection speeds of 861 µs/710 µs (rise/fall time) as opposed to non-rippled devices (377 ms/392 ms). The results demonstrate a facile, cost-effective, and large-area method to dope amorphous Ga2O3 films in a bottom-up approach which may be employed for increasing the electrical conductivity of other amorphous oxide semiconductors as well.

The SFTSV Nonstructural Proteins Induce Autophagy to Promote Viral Replication via Interaction with Vimentin.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified phlebovirus associated with severe hemorrhagic fever in humans. Studies have shown that SFTSV nucleoprotein (N) induces BECN1-dependent autophagy to promote viral assembly and release. However, the function of other SFTSV proteins in regulating autophagy has not been reported. In this study, we identify SFTSV NSs, a nonstructural protein that forms viroplasm-like structures in the cytoplasm of infected cells as the virus component mediating SFTSV-induced autophagy. We found that SFTSV NSs-induced autophagy was inclusion body independent, and most phenuivirus NSs had autophagy-inducing effects. Unlike N protein-induced autophagy, SFTSV NSs was key in regulating autophagy by interacting with the host's vimentin in an inclusion body-independent manner. NSs interacted with vimentin and induced vimentin degradation through the K48-linked ubiquitin-proteasome pathway. This negatively regulating Beclin1-vimentin complex formed and promoted autophagy. Furthermore, we identified the NSs-binding domain of vimentin and found that overexpression of wild-type vimentin antagonized the induced effect of NSs on autophagy and inhibited viral replication, suggesting that vimentin is a potential antiviral target. The present study shows a novel mechanism through which SFTSV nonstructural protein activates autophagy, which provides new insights into the role of NSs in SFTSV infection and pathogenesis. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerging tick-borne pathogen that causes multifunctional organ failure and even death in humans. As a housekeeping mechanism for cells to maintain steady state, autophagy plays a dual role in viral infection and the host's immune response. However, the relationship between SFTSV infection and autophagy has not been described in detail yet. Here, we demonstrated that SFTSV infection induced complete autophagic flux and facilitated viral proliferation. We also identified a key mechanism underlying NSs-induced autophagy, in which NSs interacted with vimentin to inhibit the formation of the Beclin1-vimentin complex and induced vimentin degradation through K48-linked ubiquitination modification. These findings may help us understand the new functions and mechanisms of NSs and may aid in the identification of new antiviral targets.

The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

The effects of vitamin D intake and status on symptom severity and quality-of-life in adults with irritable bowel syndrome (IBS): a systematic review and meta-analysis.

IMPORTANCE: Many individuals with irritable bowel syndrome (IBS) have insufficient or deficient serum 25-hydroxyvitamin D [25(OH)D] status; however, it is not clear if improved vitamin D nutritional status through higher intake can improve symptom severity and quality of life. OBJECTIVE: This systematic review and meta-analysis aimed to identify if changes in vitamin D intake or status affect symptom severity and quality of life in adults with IBS.Data Sources: MEDLINE®, Cochrane Central Register of Controlled Trials, Global Health, EMBASE, and Web-of-Science databases were systematically searched for relevant articles to August 12, 2024, in the English language.Study Selection: Clinical trials, prospective observational studies, and Mendelian randomization (MR) analyses reporting the effect of vitamin D intake or status on IBS-related outcomes were included.Data Extraction and Synthesis: Article review and data extraction were conducted by 2 authors following the PRISMA guidelines. Random effects meta-analyses and the Nutrition Quality Evaluation Strengthening Tools to assess risk of bias were employed for randomized controlled trials.Main Outcome(s) and Measure(s): Primary outcomes included measures of serum 25(OH)D status, symptom severity, and quality of life. RESULTS: 12 studies from 15 articles were included (n = 7 RCTs; n = 3 single-arm interventions; n = 2 MR). Seven study populations had deficient (<20 ng/mL) and three had insufficient (21-29 ng/mL) baseline serum 25(OH)D status. RCTs measured changes in serum 25(OH)D after 6-26 wks with 3,000 IU daily to 50,000 IU bi-weekly vitamin D dosages. Meta-analyses of low risk-of-bias RCTs revealed increased 25(OH)D levels in groups treated with oral vitamin D compared to placebo (n = 5; Pooled mean difference [95% CI]: 20.33 [12.91, 27.74] ng/mL; I2 = 97.9%). Quality of life scores improved significantly in deficient populations (n = 3; 3.19 [2.14, 4.24]; I2 = 0.0%). Non-significant decreased trends in IBS symptom severity were shown across populations (n = 6: -25.89 [-55.26, 3.48]; I2 = 92.8%). CONCLUSION: Moderate level evidence indicate vitamin D supplementation may improve status in adults with IBS and quality of life in those with deficient status at baseline.

QUESTION: Do changes in vitamin D intake or status affect symptom severity and quality of life in adults with irritable bowel syndrome?FindingsIn this systematic review and meta-analysis, moderate level evidence supports vitamin D supplementation for improving serum 25-hydroxyvitamin D status in adults with IBS and for increasing quality of life scores in those with deficient status at baseline.Meaning: Vitamin D supplementation may improve quality of life in IBS patients with deficient serum 25-hydroxyvitamin D status.

Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Cognitive function in patients with irritable bowel syndrome: impairment is common and only weakly correlated with depression/anxiety and severity of gastrointestinal symptoms.

OBJECTIVE: To investigate cognitive function in patients with irritable bowel syndrome (IBS) and its relation to anxiety/depression and severity of gastrointestinal (GI) symptoms. METHODS: Patients with IBS (n = 65) and healthy controls (HCs, n = 37) performed the ten subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Age-normed index scores of five cognitive domains (Immediate memory, Visuospatial function, Language function, Attention, Recall) and a total (Fullscale) score were derived from the performance. Emotional function was assessed using the Hospital Anxiety and Depression Scale (HADS), and the IBS Symptom Scoring System (IBS-SSS) was used to define the severity of GI symptoms. RESULTS: Patients with IBS reported significantly higher scores than the HC group on symptom measures of anxiety and depression, and significantly lower scores on the Immediate memory, Recall, and Fullscale RBANS indexes. Approximately 30% of the IBS patients obtained index scores at least one standard deviation below the population mean, and more than 50% scored above the screening threshold for an anxiety disorder. The severity of GI symptoms was significantly correlated with the severity level of anxiety symptoms (p=.006), but neither the severity level of emotional nor GI symptoms was significantly correlated with the RBANS index scores in the IBS group. CONCLUSION: Cognitive and emotional function were more severely affected in patients with IBS than in HCs. The weak correlation between the two functional areas suggests that both should be assessed as part of a clinical examination of patients with IBS.

Cognitive and emotional function should be assessed in patients with IBS.Cognitive impairment was less closely related to symptoms of anxiety/depression and severity of GI symptoms than expected.An independent contribution of both emotional symptoms and cognitive function should be considered when developing treatment programs for patients with IBS.

Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome.

BACKGROUND: Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). METHODS: We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. RESULTS: Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. CONCLUSIONS: Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

Overweight and vitamin D deficiency are common in patients with irritable bowel syndrome - a cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disease with unknown etiology. Poor dietary intake with nutritional deficiency and overweight have been described to increase the risk of IBS. The aim of the present study was to compare weight and circulating levels of micronutrients in IBS compared with healthy controls. DESIGN: Cross-sectional study. METHODS: Patients diagnosed with IBS and healthy volunteers were recruited. Participants had to complete a dietary diary book and the questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). Weight and height were measured, and blood samples were drawn. C-reactive protein (CRP), cobalamin, folate, iron, total iron-binding capacity (TIBC), and 25-hydroxy (25-OH) vitamin D were analyzed. Differences were calculated between groups and generalized linear model for regressions was adjusted for false discovery rate (FDR). RESULTS: IBS patients (n = 260) were elder than controls (n = 50) (44.00 (33.25-56.00) vs. 37.85 (30.18-45.48) years; p = 0.012). After adjustment for age, both weight (ß: 5.880; 95% CI: 1.433-10.327; p = 0.010, FDR = 0.020) and body mass index (BMI) (ß: 2.02; 95% CI: 0.68-3.36; p = 0.003, FDR = 0.012) were higher in patients. Among IBS participants, 48.1% were overweight/obese compared with 26.0% in controls (p = 0.007). Diarrhea-predominated IBS had highest weight (p < 0.001) and BMI (p = 0.077). CRP and cobalamin were higher in patients than controls (p = 0.010 vs. p = 0.007), whereas folate was highest in controls (p = 0.001). IBS patients had lower intake of vegetables (p = 0.026), dairy products (p = 0.004), and cereals (p = 0.010) compared with controls. Despite 21.5% of IBS patients were taking vitamin D supplements, 23.65% of them had vitamin D levels below 50 nmol/L, compared with 26.0% observed in the control group (p = 0.720). Vitamin D levels were lower in overweight than in normal weight IBS patients (60 (48-73) nmol/L vs. 65 (53-78) nmol/L, p = 0.022). Vitamin D correlated with cobalamin and folate but correlated inversely with TIBC and BMI. IBS patients had a high degree of gastrointestinal and extraintestinal symptoms, which were inversely associated with iron levels. Extraintestinal symptoms were associated with increased BMI. CONCLUSION: IBS patients were often overweight or obese, with low vitamin D levels. High burden of extraintestinal symptoms were associated with overweight and lower iron levels. REGISTRATION: ClinicalTrials.gov, NCT05192603 (Date of registration 11/29/2021) and NCT03306381 (Date of registration 09/18/2017), respectively.

Decoding IBS: a machine learning approach to psychological distress and gut-brain interaction.

PURPOSE: Irritable bowel syndrome (IBS) is a diagnosis defined by gastrointestinal (GI) symptoms like abdominal pain and changes associated with defecation. The condition is classified as a disorder of the gut-brain interaction (DGBI), and patients with IBS commonly experience psychological distress. The present study focuses on this distress, defined from reports of fatigue, anxiety, depression, sleep disturbances, and performance on cognitive tests. The aim was to investigate the joint contribution of these features of psychological distress in predicting IBS versus healthy controls (HCs) and to disentangle clinically meaningful subgroups of IBS patients. METHODS: IBS patients ( n = 49 ) and HCs ( n = 28 ) completed the Chalder Fatigue Scale (CFQ), the Hamilton Anxiety and Depression Scale (HADS), and the Bergen Insomnia Scale (BIS), and performed tests of memory function and attention from the Repeatable Battery Assessing Neuropsychological Symptoms (RBANS). An initial exploratory data analysis was followed by supervised (Random Forest) and unsupervised (K-means) classification procedures. RESULTS: The explorative data analysis showed that the group of IBS patients obtained significantly more severe scores than HCs on all included measures, with the strongest pairwise correlation between fatigue and a quality measure of sleep disturbances. The supervised classification model correctly predicted belongings to the IBS group in 80% of the cases in a test set of unseen data. Two methods for calculating feature importance in the test set gave mental and physical fatigue and anxiety the strongest weights. An unsupervised procedure with K = 3 showed that one cluster contained 24% of the patients and all but two HCs. In the two other clusters, their IBS members were overall more impaired, with the following differences. One of the two clusters showed more severe cognitive problems and anxiety symptoms than the other, which experienced more severe problems related to the quality of sleep and fatigue. The three clusters were not different on a severity measure of IBS and age. CONCLUSION: The results showed that psychological distress is an integral component of IBS symptomatology. The study should inspire future longitudinal studies to further dissect clinical patterns of IBS to improve the assessment and personalized treatment for this and other patient groups defined as disorders of the gut-brain interaction. The project is registered at https://classic. CLINICALTRIALS: gov/ct2/show/NCT04296552 20/05/2019.

The causal relationship between cholecystectomy and IBD/IBS and the role of bile acids and gut microbiota: a two-sample Mendelian randomization study.

OBJECTIVE: This study aims to explore the causal relationship between cholecystectomy and inflammatory bowel disease (IBD)/irritable bowel syndrome (IBS) and the role of serum bile acids and gut microbiota in this context. METHODS: Utilizing genetic variant data from previous Genome-Wide Association Studies (GWAS), this study employed a two-sample MR approach to assess the causal effect of cholecystectomy on IBD/IBS. RESULTS: The MR analysis suggested a potential negative causal relationship between cholecystectomy and UC (p = 0.0233, OR 0.9773, 95%CI 0.9581-0.9969) and a positive causal relationship between cholecystectomy and IBS (p = 0.0395, OR 4.077, 95%CI 1.0699-15.5362). Various sensitivity analyses reinforced the reliability of the causal relationship. However, the analysis did not find definitive results between serum bile acids or gut microbiota and cholecystectomy or IBD/IBS, possibly due to insufficient statistical power. MVMR find a causal relationship between bile acids and IBS (p = 0.0015, b = 0.4085) and UC (p = 0.0198, b = 0.0029). CONCLUSION: This study provides evidence of a causal relationship between cholecystectomy and IBD/IBS, highlighting the potential risk reduction for UC and increased risk for IBS following cholecystectomy. The role of bile acids and gut microbiota in this relationship remains unclear, necessitating further research to validate the causality and explore underlying mechanisms.

Acacia fiber or probiotic supplements to relieve gastrointestinal complaints in patients with constipation-predominant IBS: a 4-week randomized double-blinded placebo-controlled intervention trial.

PURPOSE: To date, no adequate treatment for irritable bowel syndrome with predominant constipation complaints (IBS-C) is available. Fibers with prebiotic properties and probiotic compounds have shown promise in relieving IBS-C-related complaints. We aimed to determine the effects of a 4-week intervention with either an Acacia fiber (AF) with prebiotic properties or a probiotic Bifidobacterium Lactis (BLa80) supplement, compared to a control supplement, on stool pattern, IBS symptoms and Quality of Life (QoL), in IBS-C individuals. METHODS: A parallel, double-blind, randomized controlled trial involving 180 subjects meeting the ROME IV criteria for IBS-C was conducted. Following a 4-week observation period, subjects received either AF (10 g), Probiotic BLa80 (4 g; 2 × 1011 CFU/g) or a maltodextrin placebo (10 g) daily for 4 weeks. Subjects reported daily information on stool pattern and gastrointestinal complaints. Before and after each 4-week period, questionnaires on symptom severity, constipation symptoms, anxiety and depression and QoL were completed. Stool mass was measured for 5-days before and after the intervention. RESULTS: Stool frequency significantly improved in the AF and Probiotic BLa80 groups compared to placebo (P < 0.001, P = 0.02, respectively). Probiotic BLa80 showed a significant reduction in IBS symptom severity (P = 0.03), for AF a trend towards decreased constipation symptoms (PAC-SYM, P = 0.10) was observed. No significant changes in stool consistency, stool mass or QoL measures were observed between the AF and Probiotic BLa80 compared to placebo. CONCLUSION: Daily dietary supplementation with Acacia fiber and probiotic supplements might help IBS-C patients by relieving IBS-related complaints compared to a placebo supplement. REGISTRATION NUMBER OF CLINICAL TRIAL: The trial is registered at ClinicalTrials.gov: NCT04798417: Study Details | Nutrition to Relieve IBS Constipation | ClinicalTrials.gov.

A systematic review of the association between environmental risk factors and the development of irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with roots in genetic, immune, psychological, and dietary factors. Recently, the potential correlation between environmental exposures, such as air pollution, and IBS has gained attention. This review aimed to systematically examine existing studies on environmental factors associated with IBS, elucidating this interplay and guiding future research. METHODS: A literature search was conducted in Medline, EMBASE, Scopus, and Cochrane databases from database inception to October 10, 2023, using the keywords "Irritable Bowel" or IBS or "Irritable Colon" or "Mucous Colitis" or "Spastic Colitis" or "Spastic Colon" AND "environment* exposure*". Studies were included if they were original, published in English, described defined environmental exposure(s), and had documented diagnosis of IBS. For the purposes of this review, articles reporting physical (e.g. radiation and climate change), biological (e.g. bacteria and viruses), and chemical (e.g. harmful gases) exposures were included while psychological and dietary factors, which have been reviewed in detail elsewhere, are outside of the scope. RESULTS: A total of seven studies focusing on air quality, microbial exposure, and other environmental factors were reviewed. Studies highlighted a potential association between air pollutants and increased IBS incidence. Microbial exposure, post-natural disaster or due to poor sanitation, was linked to IBS development and gut dysbiosis. Other exposures, such as early pet ownership, were also associated with IBS risk. CONCLUSION: Existing research demonstrates an epidemiologic relationship between environmental exposures and the development of IBS. Further research is needed to understand these associations.

Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.

The hyper-brain neural couplings distinguishing high-creative group dynamics: an fNIRS hyperscanning study.

This hyperscanning study aimed to identify a neural coupling profile that distinguishes high-creative group dynamics through functional near infrared spectroscopy. A total of 123 dyads completed one creativity task (alternative uses task, AUT) and contrast task (objective characteristics task). A K-means clustering analysis on AUT performance grouped 31/29 dyads into high/low-creative group, respectively. In comparison with the low-creative group, the high-creative group showed: (i) higher collective flexibility and delayed perspective-taking behaviors, but lower immediate perspective-taking behaviors; (ii) enhanced interpersonal brain synchronization (IBS) between the left inferior frontal gyrus (lIFG) and right motor cortex, and nodal Eloc at the right superior temporal gyrus (rSTG); (iii) declined intrapersonal functional connectivity between the right angular gyrus (rAG) and rSTG, and IBS between the lIFG and rAG. The enhanced neural couplings positively correlated with group creative performance, whereas a reverse correlation pattern existed in the declined ones. A leave-one-out cross-validation analysis showed these neural couplings reliably predicted group creative performance within the sample. These indicate that high-creative group dynamics are characterized by utilizing partners' shared information when necessary (e.g. encountering idea exhaustion). A neural coupling profile consisting of sophisticated interplays between regions within frontal, temporal, and parietal lobes may underlie high-creative creative dynamics.