Decoding the Gut-Brain Axis: A Journey toward Targeted Interventions for Disorders-of-Gut-Brain Interaction.Digestive diseases (Basel, Switzerland) • December 20, 2024
Gerald Holtmann, Md Moniruzzaman, Ayesha Shah
Background: The gut-brain axis is a bidirectional communication pathway connecting the gastrointestinal tract and the brain. Disorders of gut-brain interaction (DGBI) manifest as highly prevalent gastrointestinal disorders such as irritable bowel syndrome (IBS) or functional dyspepsia (FD).
Conclusions: The initial focus of DGBI research was on the effects of psychological stress on digestive functions like gastrointestinal motility, or secretion of gastric acid and pancreatic enzymes. Concepts related to DGBI have expanded in recent decades. Activation of mucosal or systemic immune functions has been observed in DGBI, and it is established that the gastrointestinal microbiome can alter mucosal integrity and permeability, leading to pro-inflammatory cytokine release that affects brain function. Pharmacologic treatments (e.g., tricyclic antidepressants) and non-pharmacologic interventions (e.g., cognitive behavioral therapy) are now standard for DGBI patients. Advances in culture-independent methods to study gastrointestinal microbes reveal new insights into DGBI and gut microbiota appear to play a crucial role in modulating the gut-brain axis and regulating various bodily functions. Conclusions: DGBI are highly prevalent. Research in this field has evolved from studying the effects of psychological stress to recognizing the significant role of the gut microbiome and its metabolites in mucosal integrity and immune responses.
Mechanisms of action and clinical effectiveness of herbal treatments for disorders of gut-brain interaction.Digestive And Liver Disease : Official Journal Of The Italian Society Of Gastroenterology And The Italian Association For The Study Of The Liver • March 19, 2025
Md Moniruzzaman, Ayesha Shah, Mark Morrison, Natasha Koloski, Kok Gwee, Minhu Chen, Yongsung Kim, Kana Ayaki, Thomas Efferth, Gerald Holtmann
Disorders of gut-brain interaction (DGBI), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS), affect about one-third of the global population. Many patients turn to traditional and herbal medicines for relief, given the lack of effective therapies. This review assesses the clinical and preclinical evidence for herbal treatments used for patients with DGBI. Placebo-controlled trials show that specific herbal preparations, including peppermint oil, ginger, and commercial formulations like STW-5, ZZKZ and Rikkunshito significantly improve gastrointestinal symptoms. Their effectiveness likely arises from various mechanisms, such as alterations in gastrointestinal motility, desensitization of visceral sensory function, and suppression of low-grade mucosal or systemic inflammation. Recent studies of the effects of herbal extracts on the gastrointestinal microbiome also implicate microbial involvement in their effectiveness. Most herbal preparations contain multiple bioactive compounds to address various disease mechanisms, and there remains a significant gap in dose-response studies for optimizing therapeutic outcomes.
Investigating participation in the Australian National Bowel Cancer Screening Program through general practice: a survey on practices, challenges and digital opportunities.Public Health Research & Practice • February 20, 2025
Nicole Marinucci, Natasha Koloski, Amanda Whaley, Rachael Bagnall, Ayesha Shah, Belinda Goodwin, Gerald Holtmann
Objectives Promoting the Australian National Bowel Cancer Screening Program in general practice has been identified as an effective strategy to increase participation rates. Despite the positive influence general practitioners (GPs) have on patient decision-making, program endorsement is not routinely included within the national program's policy and practice. The aim of this study was to gain a comprehensive understanding of knowledge, health promotion strategies and the challenges/opportunities for general practice staff to support patient participation and navigation through the National Bowel Cancer Screening Program pathways. Study type A 52-item online cross-sectional survey. Methods A total of 320 general practice clinics in the Metro South Hospital and Health Service, Queensland, Australia received a direct invitation via email to participate. The survey contained items on knowledge, health promotion strategies and challenges/opportunities to endorse participation in the National Bowel Cancer Screening Program, including enquiry about the utilisation of electronic medical records. Results Eighty-eight individuals participated, including GPs, practice managers and practice nurses. Of GPs, 96.2% indicated they were likely to promote the National Bowel Cancer Screening Program to patients. Few participants used systems to identify/notify patients due for screening, and over half indicated that Medicare reimbursements (56.8%) and electronic systems for identifying eligible or overdue patients (53.4%) would support their ability to promote the National Bowel Cancer Screening Program in routine practice. Conclusion Early detection and treatment of bowel cancer is a public health priority in Australia and internationally. Findings highlight the willingness of staff to promote participation; however, the need for incentivisation and streamlined software integration to identify and prompt eligible patients to screen through the National Bowel Cancer Screening Program remains. These findings contribute new evidence regarding the resources, preferences and system-level requirements needed to support routine GP endorsement of the National Bowel Cancer Screening Program.
Economic Evaluations of Non-Pharmacological Interventions for Treating Disorders of Gut-Brain Interaction: A Scoping Review.November 04, 2024
Anton Pak, Madeline O'grady, Gerald Holtmann, Ayesha Shah, Haitham Tuffaha
Objective: Disorders of gut-brain interaction are highly prevalent and burdensome conditions for both patients and healthcare systems. Given the limited effectiveness of pharmacotherapy in treating disorders of gut-brain interaction, non-pharmacological interventions are increasingly used; however, the value for money of non-pharmacological treatments is uncertain. This is the first review to assess the economic evaluation evidence of non-pharmacological interventions for disorders of gut-brain interaction.
Methods: A scoping review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Reporting adhered to ISPOR's good practices for systematic reviews with cost and cost-effectiveness outcomes. Comprehensive searches were performed on 24 October, 2023, and an updated search was run on 18 May, 2024 in PubMed/MEDLINE, Embase, Web of Science, Scopus and the International HTA database, with two reviewers screening studies in parallel. The novel Criteria for Health Economic Quality Evaluation (CHEQUE) framework was used to assess methodological and reporting quality. Reporting quality was further assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022.
Results: Fifteen studies were included. Most studies examined treatments for irritable bowel syndrome. Cognitive behavioural therapy, dietary interventions and sacral neuromodulation were cost effective. Acupuncture and physiotherapy were not. CHEQUE assessment showed 12 studies met at least 70% of the methodological criteria, and 14 studies achieved 70% or more for reporting quality.
Conclusions: This review highlights gaps in the current evidence base, particularly in the robustness and generalisability of results due to methodological inconsistencies. Future research should incorporate longer follow-ups, comprehensive cost assessments, subgroup analyses, equity considerations and clearer justifications for modelling assumptions.
Small intestinal bacterial overgrowth in chronic liver disease: an updated systematic review and meta-analysis of case-control studies.EClinicalMedicine • September 08, 2024
Ayesha Shah, Liam Spannenburg, Parag Thite, Mark Morrison, Thomas Fairlie, Natasha Koloski, Purna Kashyap, Mark Pimentel, Ali Rezaie, Gregory Gores, Michael Jones, Gerald Holtmann
Small Intestinal Bacterial Overgrowth (SIBO) has been implicated in the pathophysiology of chronic liver disease (CLD). We conducted a systematic review and meta-analysis to assess and compare the prevalence of SIBO among CLD patients (with and without with complications of end stage liver disease) and healthy controls. Electronic databases were searched from inception up to July-2024 for case-control studies reporting SIBO in CLD. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with CLD and controls were calculated utilizing a random-effects model. The protocol was prospectively registered with PROSPERO (CRD42022379578). The final dataset included 34 case-control studies with 2130 CLD patients and 1222 controls. Overall, the odds for SIBO prevalence in CLD patients compared to controls was 6.7 (95% CI 4.6-9.7, p < 0.001). Although the prevalence of SIBO among patients with CLD with cirrhosis was higher at 42.9% (95% CI: 35.9-50.2) compared to 36.9% (95% CI: 27.4-47.6) in those without cirrhosis, this difference failed statistical significance. However, CLD patients with decompensated cirrhosis had a significantly higher prevalence of SIBO compared to those with compensated cirrhosis, with an OR of 2.6 (95% CI: 1.5-4.5, p < 0.001). Additionally, the prevalence of SIBO was significantly higher in CLD patients with portal hypertension (PHT) than in those without PHT, with an OR of 2.1 (95% CI: 1.4-3.1, p < 0.001). The highest prevalence of SIBO was observed in patients with spontaneous bacterial peritonitis (SBP) (57.7%, 95% CI 38.8-74.5), followed by patients with hepatic encephalopathy (41.0%, 95% CI 16.0-72.3) and patients with variceal bleed (39.5%, 95% CI 12.1-75.6). Overall, there is a significantly increased prevalence of SIBO in CLD patients compared to controls. The prevalence is even higher in CLD patients with PHT, especially those with SBP. This meta-analysis suggests that SIBO is associated with complications of CLD and potentially linked to the progression of CLD. National Health and Medical Research Council, Centre for Research Excellence (APP170993).
