A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.

OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I2 = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I2 = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I2 = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I2 = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I2 = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting. DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.

Irritable bowel syndrome: Clinical practice update.

ABSTRACT: Irritable bowel syndrome (IBS) is a common and burdensome disorder characterized by chronic recurrent abdominal pain and altered bowel habits. IBS remains misunderstood, leading to delayed diagnosis, impaired quality of life, and substantial healthcare costs. Advancing clinicians' understanding of this complex biopsychosocial process, using a positive diagnostic strategy rather than a diagnosis of exclusion, and incorporating a multimodal treatment approach expedite time to diagnosis, facilitate symptom relief, and reduce financial expenditure.

The Microbiome and Irritable Bowel Syndrome: An Emerging Hope for Treatment.

Irritable bowel syndrome is a gastrointestinal disorder that affects 15%-20% of the US population. Its symptoms can have negative effects on a person's quality of life, and its treatment can be associated with high medical costs. An emerging area of irritable bowel syndrome research concerns the relationship between this condition and the gut microbiome. The purpose of this article is not only to review irritable bowel syndrome, and the role that the microbiome can play in its symptoms, but also to examine new emerging pathways that could blaze the trail for more individualized treatments. If equipped with this knowledge, gastrointestinal nurses and providers of care can be better prepared to help patients with irritable bowel syndrome in order to manage symptoms and improve their quality of life.

Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis.

CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.

Unresolved conundrum of the role of physical activity in inflammatory bowel disease: What next?

There is considerable controversy on the role of physical activity in irritable bowel disease (IBD) since published reports are conflicting. It is well known that there is known relapse with specific treatment in IBD. This, in addition to onset of extraintestinal symptoms creates a need to think of alternate approaches. In this context, the current article describes the need of a multi-institutional study with standard protocol of physical activity for documenting its effect on both the primary disease and the extra alimentary manifestations. This paper also points out the possibility of using adjuvant complementary medicine such as yoga, whose effects have been documented in other diseases like irritable bowel syndrome. A third approach could be to focus on the intestinal dysbiosis in IBD and concentrate on research on restoring the microbial flora to normal, to see whether the extra-intestinal symptoms are alleviated.

Real-world outcomes for a digital prescription mobile application for adults with irritable bowel syndrome.

BACKGROUND: Mahana™ IBS is a Food and Drug Administration-cleared prescription mobile application designed to deliver 3 months of gut-directed cognitive behavioral therapy (CBT) to adults ≥22 years old with irritable bowel syndrome (IBS). We assessed whether gut-directed CBT delivered digitally improved outcomes in IBS management. METHODS: We studied users who had a dispensed physician prescription for Mahana™ IBS between August 2021 and August 2023. The primary outcome was change in IBS symptom severity (IBS-SSS) score. KEY RESULTS: For the 843 patients, 324 (38%) completed half of the program up to session 5, and 162 (19%) of participants completed the full program up to session 10. Median age was 41 years, median IBS-SSS was 270 (moderate severity), IBS-mixed subtype was most common (23%) followed by IBS-C (20%) and IBS-D (19%). The change in IBS-SSS was -81.0 (p = < 0.001) after session 5 and - 104.4 (p = < 0.001) after session 10. In multivariate analyses, a higher baseline IBS-SSS (OR 1.59; 95% CI 1.26-2.01) and high baseline Perceived Stress Scale (PSS) score predicted non-response (OR 0.95; 95% CI 0.91-0.98) while older age (OR 1.10 per decade; 95% CI 1.01-1.20), prescription source from a healthcare provider (as opposed to third party telehealth encounter, OR 1.48; 95% CI 1.07-2.05), and payment for the app (OR 1.93; 95% CI 1.41-2.63) predicted adherence. CONCLUSIONS & INFERENCES: Use of a digital mobile application for gut-directed CBT improved symptoms of IBS. Digital health applications have the potential to democratize CBT and allow integrated care to scale for patients with IBS.

Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

Mechanisms of Peitu Yimu acupuncture in repairing intestinal mucosal barrier by regulating CRF/CRFR1 pathway in diarrhea-predominant irritable bowel syndrome rats. / 培土抑木针法调节CRF/CRFR1é€šè·¯ä¿®å¤è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ è‚ é»è†œå±éšœçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the effect of Peitu Yimu(strengthening spleen and soothing liver) acupuncture on intestinal mucosal barrier function and corticotropin-releasing factor (CRF)/CRF receptor 1 (CRFR1) pathway in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in alleviating IBS-D. METHODS: Forty female SD rats were randomly divided into blank, model, electroacupuncture (EA), and agonist groups, with 10 rats in each group. Except for the blank group, rats in the other groups were given folium sennae infusion by gavage combined with chronic unpredictable mild stress to establish IBS-D model. Rats in the EA group received acupuncture at "Tianshu"(ST25) and EA at "Zusanli"(ST36) and "Taichong"(LR3) (2 Hz/15 Hz) on one side for 20 min, with the side chosen alternately every other day, for 14 days after modeling. Rats in the agonist group received acupuncture 30 min after intravenous injection of CRFR1 agonist urocortin, with the same manipulation method and time as the EA group. Before and after intervention, visceral pain threshold and stool Bristol scores were measured. Elevated plus maze test and open field test were used to detect anxiety and depression like behavior of rats. ELISA was used to detect the contents of CRF and CRFR1 in rats serum. Immunohistochemistry was used to detect the positive expressions of CRF, CRFR1, zonula occludens protein 1(ZO-1), occlusal protein(Occludin), and closure protein 1 (Claudin-1) in colon tissue. RESULTS: Compared with the blank group, the visceral pain threshold, open arm time percentage (OT%), total distance of movement in the open field test, and positive expression of ZO-1, Occludin, and Claudin-1 in colon were decreased (P<0.01, P<0.05), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were increased (P<0.01) in the model group. After intervention and compared with the model group, the visceral pain threshold, OT%, total distance of movement in the open field test, and positive expressions of ZO-1, Occludin, and Claudin-1 in colon were increased (P<0.05, P<0.01), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were decreased (P<0.01) in the EA group；the Bristol stool scores, serum CRF content, and CRF positive expression in colon were significantly decreased in the agonist group (P<0.01). CONCLUSIONS: Peitu Yimu acupuncture can significantly improve visceral hypersensitivity and anxiety-depression state in IBS-D rats. Its mechanism may be related to the inhibition of CRF/CRFR1 pathway and restoration of intestinal tight junction protein expressions.

Gastrointestinal Conditions: Acute Infectious Gastroenteritis and Colitis.

Gastroenteritis is inflammation of the stomach and intestines; colitis is inflammation of the colon. Viruses are the most common cause, followed by bacteria and parasites. Incidence of the various infections varies by age, sex, location, and vaccine availability; vaccination has reduced rotavirus infections by as much as 90% in children. Postinfectious complications include irritable bowel syndrome (IBS) and lactose intolerance. Approximately 9% of patients with acute gastroenteritis or colitis develop postinfectious IBS, which accounts for more than 50% of all IBS cases. The diagnostic approach to gastroenteritis and colitis varies with symptom severity. Microbial studies are not needed with mild symptoms that resolve within a week, but longer-lasting or more severe symptoms (including bloody stool) warrant microbial studies. In addition, recent antibiotic exposure should prompt testing for Clostridioides difficile. Multiplex antimicrobial testing is preferred; stool cultures and microscopic stool examinations are no longer first-line tests. Management depends on severity. Patients with mild or moderate symptoms are treated with oral hydration if tolerated; nasogastric or intravenous hydration are used for those with more severe illness. In addition, antiemetic, antimotility, and/or antisecretory drugs can be used for symptom control. Antimicrobial therapy is indicated for C difficile infections, travel-related diarrhea, other bacterial infections with severe symptoms, and parasitic infections.

Manual & exercise therapy for treatment of chronic abdominal pain and diarrhea, a case report.

A 34-year-old male with a 9+ year history of right sided abdominal pain, associated diarrhea and a diagnosis of irritable bowel syndrome was referred for physical therapy and chiropractic care at a multidisciplinary primary care clinic. Multiple evaluations by various providers resulted in multiple tests and numerous medications without substantial relief in symptoms. Five physical therapy visits and three sessions of chiropractic care resulted in 90% improvement in subjective pain report and 60-70% reduction in diarrhea frequency. At a 6 month follow up phone visit, his symptoms had continued to decrease. While limited as a case study, this report may illustrate a potential somatovisceral relationship and subsequent reduction in gastrointestinal symptoms that can be addressed with conservative care.

Photobiomodulation improves acute restraint stress-induced visceral hyperalgesia in rats.

The purpose of this study is to explore the potential application of photobiomodulation to irritable bowel syndrome. We established the following experimental groups: the Non-Stress + Sham group, which consisted of rats that were not restrained and were only subjected to sham irradiation; the Stress + Sham group, which underwent 1 hour of restraint stress followed by sham irradiation; and the Stress + Laser group, which was subjected to restraint stress and percutaneous laser irradiation bilaterally on the L6 dorsal root ganglia for 5 minutes each. The experiment was conducted twice, with three and two laser conditions examined. Following laser irradiation, a barostat catheter was inserted into the rat's colon. After a 30-minute acclimatization period, the catheter was inflated to a pressure of 60 mmHg, and the number of abdominal muscle contractions was measured over a 5-minute period. The results showed that photobiomodulation significantly suppressed the number of abdominal muscle contractions at average powers of 460, 70, and 18 mW. However, no significant suppression was observed at average powers of 1 W and 3.5 mW. This study suggests that photobiomodulation can alleviate visceral hyperalgesia induced by restraint stress, indicating its potential applicability to irritable bowel syndrome.

Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives.

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.

Effectiveness of a Balanced Nine-Strain Synbiotic in Primary-Care Irritable Bowel Syndrome Patients-A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial.

The aim of the study was to characterize effects of a multi-strain synbiotic in patients with moderate to severe irritable bowel syndrome (IBS) of all stool form types. A total of 202 adult IBS patients were randomized (1:1) and after a four-week treatment-free run-in phase and were treated either with the synbiotic or a placebo for 12 weeks. The primary endpoints were the assessment of the severity of IBS symptoms (IBS-SSS) and the improvement of IBS global symptoms (IBS-GIS). Secondary endpoints comprised adequate relief (IBS-AR scale), stool form type (Bristol Stool Form Scale), bowel movements, severity of abdominal pain and bloating, stool pressure, feeling of incomplete stool evacuation, and adverse events. A total of 201 patients completed the study. Synbiotic treatment, in comparison to placebo, significantly improved IBS-SSS and IBS-GIS scores. At the end of the treatment, 70% of patients in the synbiotic group achieved adequate relief. After 12 weeks of treatment, the secondary endpoints were favorably differentiated in the synbiotic group when compared with the placebo group. Two patients in the synbiotic group reported transient adverse events (headache). The results indicate that treatment of IBS patients with the synbiotic significantly improved all major symptoms of IBS and was well-tolerated. The ClinicalTrials.gov registration was NCT05731232.

Integrated Virtual Care for Irritable Bowel Syndrome: A Qualitative Study.

Irritable bowel syndrome (IBS) is a condition that affects approximately one in 10 people in the United States (Defrees & Bailey, 2017). Despite the high prevalence of IBS, the medical community struggles to effectively understand, diagnose, and treat this disorder (Ankersen et al., 2021). In recent years, an increasing number of health-tech companies have emerged to offer integrated treatment of IBS via telemedicine. This pilot study explores the patient experience of virtual, multidisciplinary IBS care through a U.S.-based company, Oshi Health. Semistructured interviews were conducted followed by thematic analysis to identify commonalities between patient experience and perspective (Van Manen, 2014). Overarching themes were identified as follows: loss of the grocer, a broken system, and the power of self-trust. Although several limitations exist, including small sample size, the study offers insight into the experience of telemedicine services for IBS and provides a framework for future research.

The impact of transcutaneous electrical acustimulation (TEA) on rectal distension-induced pain in patients with irritable bowel syndrome (IBS)-A study to determine the optimal TEA delivery modalities and effects on rectal sensation and autonomic function.

BACKGROUND: Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function. METHODS: Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment. KEY RESULTS: Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04). CONCLUSIONS & INFERENCES: TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome.

To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) (p < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.

What is already known on this topicIBS is a chronic functional gastrointestinal disorder characterized by abdominal pain, bloating and abnormalities in stool frequency or form. The gut microbiota of people living with IBS differs markedly to the microbiota of healthy individuals. Gut microbiota may play a key role in IBS aetiology and IBS symptoms may be alleviated by modulating the gut microbiota. Several proposed ways to modulate gut health include normalizing the gut microbiota, preventing the overgrowth of pathogenic bacteria, modulating visceral afferent pathways, and enhancing intestinal barrier function. However, significant heterogeneity between studies, study quality and population, study design and concerns about sample size have limited national and supranational bodies from recommending probiotics for IBS. Further well-powered, randomized, repeatable and controlled trials are warranted.What this study addsThe results of this study substantially contribute to the IBS research field, firstly by providing clinically meaningful and statistically significant results from a rigorous, well designed randomized, placebo-controlled trial and secondly, by exploring the use of postbiotics in IBS, an area of research still in its infancy. Probiotic (ES1) and postbiotic (HT-ES1) supplementation significantly reduced IBS symptom severity scores compared to placebo. This study met primary and secondary outcomes and strongly suggest that ES1 and HT-ES1 could be beneficial in the management of IBS.How this study might affect research, practice, or policyThis study adds to the current evidence base, supporting the use of probiotic/postbiotics for IBS. This research could be used to inform health professionals about using probiotics in IBS and help improve the quality of life and wellbeing for people living with the condition.

A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study's aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus-containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk.