Role of Bacillus coagulans (Heyndrickxia coagulans)BCP92 in managing irritable bowel syndrome: A randomized, double-blind, multicenter, placebo-controlled clinical trial

Abstract

Background:

Irritable bowel syndrome (IBS) is a major global healthcare burden that requires effective and well-tolerated intervention. This study aimed to investigate the effectiveness and safety of Bacillus coagulans BCP92, a probiotic, in managing IBS symptoms.

Methods:

This randomized controlled trial included 100 participants who strictly adhered to the protocol. Various parameters such as IBS severity, digestive symptom frequency, gastrointestinal symptom frequency, stool consistency, interleukin-6 levels, stress relief, and anxiety levels were evaluated over 12 weeks.

Results:

B. coagulans BCP92 significantly improved IBS severity (P < .001), and gastrointestinal symptom frequency (P < .001) compared with that in the control group. The stool consistency significantly improved (P < .001). Mental stress relief was remarkable (P = .001), differentiating the test and control groups. No significant change in interleukin-6 levels was observed; however, the safety assessment revealed an excellent profile with no reported severe adverse events.

Conclusion:

B. coagulans BCP92 is one of the most promising therapeutic options for the management of IBS because it has shown significant efficacy in alleviating symptoms among patients suffering from this condition, resulting in improved stool consistency changes in addition to improving overall mental well-being for its users, thereby foreseeing the elimination of any potential side effects experienced during the implementation of this approach strategy within our health care system, thereby improving patient outcomes and leading to individualization of treatment plans among all individuals diagnosed with this disease entity who may have symptoms, including abdominal pain or discomfort associated with changes in bowel habits.

1. Introduction

Irritable bowel syndrome (IBS) is a chronic digestive disorder that affects people all over the world., a common gastrointestinal (GI) disease that triggers abdominal pain and altered bowels, affecting ~15% of the global population.^[1] In India, its prevalence ranges from 4.2% to 7.5%.^[2] IBS has a significant impact on patients’ quality of life^[3] and increases healthcare costs; however, current treatment options are often ineffective. Various treatments are available for IBS, which can help relieve the symptoms. These treatments include antidiarrheal, antispasmodic, linaclotide, laxative, and rifaximin treatments. Although these drugs can provide temporary relief, pharmacological treatments for IBS may not always be successful and their prolonged use can cause adverse side effects.^[4–6] Since its pathogenesis involves complex factors, such as gut dysbiosis, visceral hypersensitivity, altered gut motility, and numerous others it is difficult to develop effective drugs against it.^[7] Although doctors often employ dietary interventions, they sometimes make things worse for the patients. Therefore, new therapeutic approaches are under development.^[8]

Alterations in intestinal microflora play an important role in the pathogenesis of IBS.^[9–11] The shift from a healthy and diverse gut microbiome to a dysbiotic state, leading to bacterial imbalance, is increasingly linked to this disorder.^[12,13] This understanding opens up opportunities for probiotics and live microorganisms that confer health benefits as promising strategies for managing IBS.

Probiotics have various advantages related to IBS and their use can help manage different aspects of the condition.^[14] Among the many probiotic strains available, Bacillus coagulans (recently renamed as Weizmannia coagulans then again renamed as Heyndrickxia coagulans^[15]) appears to be the most promising candidate for IBS management.^[16] B. coagulans is a spore-forming probiotic with inherent advantages such as stability; resistance to harsh gastric conditions which guarantees its survival when it reaches your intestine; ability on top of. Several studies have suggested that probiotics have therapeutic potential for the treatment of digestive disorders, such as IBS, inflammatory bowel disease, lactose intolerance, and antibiotic-associated diarrhea.^{[1,14,17–19]} B. coagulans administration has been shown to alleviate IBS symptoms, including abdominal pain and bloating, altered bowel habits, dysbiosis, and stabilization of the gut microbiota.^[16]

Based on existing research findings and the known benefits of using B. coagulans this study was designed to evaluate the effectiveness of a specific strain, B. coagulans BCP92, in controlling IBS symptoms. The primary objective of this study was to determine how B. coagulans BCP92 affects various IBS symptoms such as complete relief and stool consistency. Moreover, the safety and tolerability of this probiotic intervention were considered.

2. Materials and methods

This study was conducted in 2 centers in India: Gastrocare, Liver & Digestive Disease Center, Bhopal; and Roy Nursing Home, Siliguri.

2.1. Study population

This study used perspective, randomization (computer-generated), parallelism, and double-blinding techniques with placebos at different health facilities to establish the efficacy and safety of B. coagulans BCP92 (MTCC 25460) in managing adults with IBS. A total of 100 individuals aged 18 to 70 years were enrolled in this study. Enrolment started in April 2023, and treatment of the last subject was completed in October 2023.

2.2. Treatment arms and investigational product (IP)

Two arms were used in this study. Patients in the test arm (IP) (n = 50) received capsules containing 2 billion CFU per capsule of B. coagulans BCP92 (MTCC 25460) (isolated from soil^[20] and manufactured by Pellucid Lifesciences Pvt. Ltd., Gujarat, India) orally once daily, whereas those in the control arm (placebo) (n = 50) received placebo capsules containing maltodextrin. Both groups were advised to take their respective capsules with one cup of water on an empty stomach either 1 hour before or 2 hours after mealtime. The treatment duration was similar in both arms (84 days).

2.3. Study design, randomization blinding

This was a randomized (phase-locked software study randomizer) parallel trial in which balancing ensured equal participation in both intervention and control groups. To avoid any kind of bias, neither the subjects nor the researchers knew who received the treatment because of the double-blind procedure employed. The blinding with opaque envelopes remained intact. Various visits were conducted throughout the course of this study, including screening visits, baseline visits, and subsequent visits at weeks 4, 8, and 12, respectively. The follow-up was performed on day 90 (safety assessment).

2.4. Inclusion and exclusion criteria

The inclusion criteria consisted of variables such as patient age (18–70), physical and mental well-being (should be normal), and IBS diagnosis using the Rome IV criteria (e.g., recurrent abdominal pain at least 1 day a week for the last 3 months, associated with 2 or more of the following symptoms), which provided a diversified yet uniform subject pool for analysis. However, the exclusion criteria were defined to eliminate patients with conditions (cardiovascular disorders, hepatic disorders, GI conditions other than IBS, pregnancy, malignancy, etc.) that could interfere with the results of the study or put the participants at risk. The detailed inclusion and exclusion criteria are described in Supplement Data, Supplemental Digital Content 1, http://links.lww.com/MD/N289.

2.5. Efficacy and safety variables

The primary efficacy endpoints included changes in the severity of IBS symptoms using the IBS-Severity Scoring System (IBS-SSS)^[21] (scores to evaluate the severity of IBS: <175 for mild IBS, 175–300 for moderate IBS, and >300 for severe IBS), assessment of changes in GI symptoms using the IBS-Global Improvement Scale (IBS-GIS)^[22] on 7-point Likert scale, assessment of changes in stool consistency using the Bristol Stool Form Scale^[23] (hardest/constipated [type 1] to the softest/diarrheal [type 7]), digestive symptom frequency questionnaire (DSFQ)^[24] on 5-point Likert scale (0 = never, 1 = <1 episode/wk; 2 = <3 episodes/wk; 3 = >3 episodes/wk; 4 = daily episodes), changes in interleukin-6 (IL-6) levels (The ADVIA Centaur IL6 assay), and Perceived Stress Scale (PSS-10).^[25] Safety assessments encompass adverse event recording, monitoring vital signs, and conducting physical examinations based on World Health Organization criteria.

2.6. Statistical analysis

The research methodology used mixed-effects models, 2-sample t tests for comparative analysis, and χ² tests for categorical outcomes, and the P value was based on analysis of covariance (ANCOVA). The differences between the treatment groups on the primary outcome (i.e., IBS Score, SS Score, and DSFQ Score) were tested with a mixed-effects model with baseline values of response (i.e., IBS Score) as a continuous variable.

ANCOVA was used to find the difference estimate between treatment groups. The baseline values of response data will also be included here in the analysis as a covariate. To assess whether the assumptions for the were ANCOVA investigate normal quantile plots of residuals and residuals versus fitted values. ANCOVA results were presented as P values, 90% confidance interval, and unadjusted mean differences. All other categorical outcomes were analyzed as count model using the χ² test.

3. Results

This study aimed to thoroughly evaluate the impact of B. coagulans BCP92 on diverse aspects of IBS management, including demographic characteristics, symptom severity, GI symptom frequency, stool consistency, inflammatory markers, and anxiety levels. The 2 participating centers enrolled 100 participants who were equally divided into 2 groups (Fig. 1). Dosage compliance and adverse events were assessed for safety, clinical laboratory evaluation results, vital signs, and physical findings.

Figure 1.

Disposition of subjects in the study.

3.1. Demographic and other baseline characteristics

The enrolled cohort (n = 100) included a wide range of representative demographics. The absence of dropouts and protocol deviations strengthens the study’s internal validity, providing a solid foundation for subsequent analyses (Table 1).

Table 1.

Demographic distribution of ITT participants

Parameter	Placebo (n = 50)	IP (n = 50)	P value
Male (%)	33 (66)	30 (60)	.67*
Female (%)	17 (34)	20 (40)
Age (yr, mean ± STDV)	37.06 ± 12.16	36.72 ± 13.53	.89†
Height (cm, mean ± STDV)	166.02 ± 7.79	164.94 ± 7.64	.48†
Weight (kg, mean ± STDV)	64.14 ± 8.51	63.62 ± 11.30	.79†
BMI (kg/m2, mean ± STDV)	23.28 ± 2.81	23.46 ± 3.71	.78†

P < .05 shows statistical significance.

BMI = body mass index, IP = investigational product, ITT = intention to treat, STDV = standard deviation.

^*χ2.

^†Two-sample t test.

3.2. Changes in severity of IBS symptoms using IBS-SSS

The IBS-SSS, which is the primary efficacy endpoint, showed a statistically significant difference (P < .001) between the end of treatment (EOT) (138.60 ± 49.05) test arm and baseline (341.10 ± 55.49). This was sustained throughout all follow-up visits, showing a notable shift from severe IBS to mild IBS at each visit. Conversely, the control arm did not show statistical significance (baseline: 297.00 ± 40.20; EOT: 281.70 ± 48.35; P = .088), remaining moderate in severity throughout the follow-up at each visit point. The difference in EOT between the placebo and IP groups was also statistically significant (P < .001), indicating that B. coagulans BCP92 maintained its effectiveness over time (Fig. 2).

Figure 2.

Change in IBS severity symptom score from baseline to EOT. EOT = end of treatment, IBS = irritable bowel syndrome, IBS-SSS = IBS-Severity Scoring System, IP = investigational product.

3.3. Improvement or worsening of IBS-Global Symptoms using IBS-GIS

For instance, the test arm showed significant improvement (baseline: 5.26 ± 0.99, EOT: 2.86 ± 0.70, P < .001) for symptoms according to the IBS-GIS score after week 12. On the other hand, the control group also showed some changes (baseline: 5.30 ± 1.10, EOT: 4.86 ± 0.98, P = .037). This was consistently maintained at each follow-up, indicating that the test group performed better than the control group (P < .001) and that B. coagulans BCP92 was effective (Fig. 3).

Figure 3.

Change in gastrointestinal symptom rating scale from baseline to EOT. EOT = end of treatment, GIS = Global Improvement Scale, IP = investigational product.

3.4. Assessment of change in GI symptoms’ frequency using DSFQ on 5-point Likert Scale

A notable improvement in the frequency of GI symptoms was observed in the test group compared to that in the control group at week 12 (EOT), as indicated by the DSFQ. Additionally, a thorough analysis of DSFQ scores revealed significant improvements in individual symptoms, including bloating (P < .001), abdominal pain (P < .001), diarrhea, constipation (P < .001), and stomach rumbling (P < .001), nausea (P < .001), vomiting (P < .001), headache (P < .001), and anxiety (P < .001) (Table 2).

Table 2.

Change in GI symptom’s frequency using DSFQ at baseline and week 12

DSFQ parameter	Treatment arm	DSFQ score
		Baseline (mean ± SD)	Week 12 (day 84 ± 2) EOT
			Mean ± SD	P value	Difference in EOT (mean ± SD)	t ratio	95% CI
Bloating or cramping	Test	2.64 ± 1.18	1.22 ± 0.76	<.001	1.31 ± 0.15	8.85	−1.604 to −1.016
	Control	2.68 ± 1.06	2.53 ± 0.72
Abdominal pain	Test	2.82 ± 0.96	1.32 ± 0.60	<.001	1.03 ± 0.13	7.71	−1.295 to −0.7648
	Control	2.70 ± 0.91	2.35 ± 0.73
Diarrhea or constipation	Test	2.74 ± 0.94	1.14 ± 0.67	<.001	1.28 ± 0.16	8.24	−1.588 to −0.9718
	Control	2.78 ± 0.86	2.42 ± 0.87
Stomach rumbling	Test	2.28 ± 0.97	0.86 ± 0.53	<.001	0.47 ± 0.13	3.72	−0.7209 to −0.2191
	Control	1.86 ± 0.93	1.33 ± 0.67
Nausea	Test	1.22 ± 1.07	0.44 ± 0.50	<.001	0.5 ± 0.11	4.57	−0.7170 to −0.2830
	Control	1.20 ± 1.07	0.94 ± 0.59
Vomiting	Test	0.78 ± 0.86	0.22 ± 0.42	<.001	0.46 ± 0.13	3.64	−0.7111 to −0.2089
	Control	0.72 ± 0.81	0.68 ± 0.79
Headache	Test	0.82 ± 0.86	0.43 ± 0.42	<.001	0.41 ± 0.11	3.87	−0.6202 to −0.1998
	Control	0.96 ± 0.73	0.84 ± 0.62
Anxiety	Test	1.52 ± 0.74	0.74 ± 0.50	<.001	0.6 ± 0.11	5.60	−0.8128 to −0.3872
	Control	1.62 ± 0.83	1.34 ± 0.57

P < .05 shows statistical significance.

CI = confidance interval, DSFQ = digestive symptom frequency questionnaire, EOT = end of treatment, GI = gastrointestinal, SD = standard deviation.

3.5. Assessment of change in stool consistency using Bristol Stool Form Scale

Stool consistency, as measured using the Bristol Stool Chart, emerged as an important parameter for assessing the effect of B. coagulans BCP92. The test arm showed improved stool consistency from baseline (P = .4074, χ² score: 6.143, degree of freedom: −6) to week 12 (P < .001, χ² score: 31.75, degree of freedom: 4). Significant improvements were observed, indicating that the broad-spectrum intervention covered different symptom profiles (Fig. 4).

Figure 4.

Comparative Bristol stool chart baseline vs EOT. EOT = end of treatment, IP = investigational product.

3.6. Change in IL-6

In both test and control arms, IL-6 levels remained mostly unchanged (statistically non-significant) in the placebo (baseline [mean score]: 4.75 ± 3.78, EOT [mean score]: 4.60 ± 3.43, P = .835) and IP (baseline [mean score]: 4.49 ± 5.71, EOT [mean score]: 4.34 ± 2.94, P = .874), although it is a widely used systemic inflammation marker. It can be seen from here that observed changes in IBS symptoms do not correspond with any significant immunomodulation happening at the systemic level. Interpretation of a variety of inflammatory markers allows one to understand their impact, ranging from symptomatic to physiological aspects.

3.7. Change in IBS-related mental stress relief as assessed by PSS

PSS scores can provide a close-up of the well-being of participants in terms of their mental health showing gradual and significant reduction in IBS-related psychological stress among patients in the experimental arm (baseline [mean score]: 25.28 ± 5.99, EOT [mean score]: 19.76 ± 5.09, P < .001) At each follow-up, this improvement was maintained and reached statistical significance at 12 weeks. In contrast, there was no significant stress relief observed during week 12 with respect to the control arm (baseline [mean score]: 24.82 ± 6.39, EOT [mean score]: 22.86 ± 4.13, P = .07). At the end of the treatment, there was a statistically significant difference between the placebo and IP groups (P = .001). A comprehensive analysis of stress relief provided important findings regarding the overall mental state of patients with B. coagulans BCP92 (Fig. 5).

Figure 5.

Change in IBS-related mental stress relief as assessed by PSS. EOT = end of treatment, IBS = irritable bowel syndrome, IP = investigational product, PSS = Perceived Stress Scale.

3.8. Evaluation of safety

The safety evaluation involved a thorough assessment of dosing compliance, concurrent medications, adverse events, clinical laboratory parameters, vital signs, and physical findings. The safety profile of B. coagulans BCP92 was confirmed by the absence of serious adverse events (SAE) or treatment-emergent adverse events. All hematological parameters such as absolute basophils count, absolute eosinophils count, absolute lymphocyte count, absolute monocyte count, absolute neutrophils count, basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin concentration, mean corpuscular volume, monocytes, neutrophils, platelet count, red blood cell count, red cell distribution width, total white blood cell (Supplement Table 1, Supplemental Digital Content, http://links.lww.com/MD/N290, results of hematological parameters at baseline and EOT), and biochemical parameter creatinine serum, aspartate aminotransferase, alkaline aminotransferase, alkaline phosphatase, blood urea nitrogen remained in normal range at the EOT (Supplement Table 2, Supplemental Digital Content, http://links.lww.com/MD/N291. Results of biochemical parameters at baseline and EOT). However, those in whom no dropouts were reported confirmed that their overall safety was acceptable.

4. Discussion

An interventional study was conducted to examine the efficacy, safety, and tolerability of B. coagulans BCP92 (MTCC 25460) compared with placebo in adult patients with IBS. This study aimed to examine both the specific therapeutic effect of investigational probiotics and wider issues, such as challenging conventional diagnostic practices, and suggest a different way to deal with IBS that focuses on modulating the gut microbiome.

A great revelation in the research is that there is a connection between the use of antibiotics and a higher chance of developing IBS.^[26] The traditional approach to diagnosing IBS, which involves prescribing a high-fiber diet, has been found to be obsolete and counterproductive.^[27] Consequently, this study suggests that there should be a paradigm shift toward targeting healthy microbiota associated with ulcerative colitis for treatment. Probiotics, such as various strains of B. coagulans, are potentially capable of curing IBS.^[16]

B. coagulans is distinguished from other probiotic microorganisms.^[28] The outermost coating naturally protects the cell against stressors such as osmolarity, heat, dryness, and pH extremes found in the GI tract.^[29] This unique characteristic enables B. coagulans to survive gastric acid and digestive enzymes such as pepsin and pancreatin, bile salts, ions, and mucin.^[30]

The investigational strain used in these trials, referred to as B. coagulans BCP92 (MTCC 25460), underwent rigorous scrutiny to ensure its safety and efficacy. Its safety has been confirmed by the absence of antimicrobial resistance genes in various antibiotic classes. Notably, this strain lacks genes encoding unwanted metabolites including histamine, tyramine, and putrescine bioamines. Moreover, B. coagulans BCP92 does not possess virulence genes, making it safer.^[20]

Multidimensional assessment of the study included safety and tolerability. The severity of IBS, frequency of GI symptoms, stool consistency, IL-6 levels, and mental stress related to IBS were among many other aspects of the study.

The primary efficacy endpoints were carefully selected to provide a comprehensive understanding of the effects of B. coagulans BCP92 on IBS. Some questionnaires used included validated questionnaires for IBS, including the IBS-SSS, IBS-GIS, Daily Symptom and Frequency Questionnaire (DSFQ), and Bristol Stool Chart and IL-6 levels also provided additional markers for measuring the efficacy of probiotics compared with placebo.

For patients in the B. coagulans BCP92 group at the EOT, there was a statistically significant decrease in IBS severity from baseline, as indicated by improvement in the IBS-SSS. This improvement greatly contrasted with the almost no change observed in placebo patients, thus supporting the efficacy of this probiotic in mitigating severity. A similar outcome was reported in another investigation that compared a different strain of B. coagulans LBSC.^[31]

The B. coagulans BCP92 group showed a remarkable improvement in IBS-GIS scores, with overall evidence of IBS effects in the last week over the 12-week period from baseline. There was greater improvement in symptoms among patients administered B. coagulans BCP92 than among those in the placebo group at all time points after 4, 8, and 12 weeks of treatment. These results correspond with those of another study that evaluated a multi-strain probiotic preparation in patients with IBS-D, which further supports the positive impact of B. coagulans on IBS symptoms.^[32]

The DSFQ assessment showed a significant decrease in the frequency of symptoms such as bloating or cramping, abdominal pain, diarrhea or constipation, rumbling stomach, nausea, vomiting, headache, and anxiety among patients who took B. coagulans BCP92 compared to those in the control arm at week 12. In contrast, participants in the placebo group experienced more frequent rumbling stomachs and deterioration of other symptoms. These findings indicated that B. coagulans BCP92 has broad-spectrum efficacy in relieving various types of IBS pain. Rogha et al^[33] reported improvements in abdominal pain (P < .001) and diarrhea (P < .001) in 85 adult patients with IBS treated with B. coagulans. Several other studies on B coagulans GBI-30 have shown improvement in abdominal pain and bloating (P < .01) (n = 44)^[34] and improved bowel movement (P = .042) in diarrhea-predominant IBS (n = 52).^[35]

A key aspect of IBS treatment is restoration of normal stool consistency. This is supported by the findings of Gupta and Maity,^[31] who reported significant improvements in IBS-SSS (P < .0001) and DSFQ parameters, as well as stool consistency (P = .0002) in a group treated with Bacillus coagulans LBSC. In another study (n = 36) by Majeed et al,^[36] a significant decrease in clinical symptoms related to IBS was observed in a patient group that received B. coagulans MTCC 5856 (P < .01). A study conducted on Bacillus coagulans Unique IS2 reported a significant reduction in pen intensity (P < .001). Improvement in IBS Symptom severity (P < .001), stool consistency (P < .001), and serum cytokines such as IL-6 remains unchanged.^[37]

The pathophysiology of IBS remains elusive, although low-grade inflammation is implicated in its etiology, which has led to the examination of IL-6 levels.^[38] Some researchers have suggested that variations in circulating pro-inflammatory IL-6 levels and IL-6 gene polymorphisms may be involved in IBS; however, the findings of these studies are inconsistent.^{[32,37,39–41]} A systematic review/meta-analysis reported higher levels of serum IL-6 in patients with IBS than in controls, particularly in those with IBS.^[39] However, the present study indicated no significant difference from baseline until 12 weeks between the 2 groups, that is, those taking B. coagulans BCP92 and placebo groups in terms of IL-6. Such divergence questions the status quo, thus calling for further studies on the intricate relationship between inflammation and IBS pathogenesis.

The PSS was used to gauge the stress response levels of individuals with IBS. A higher PSS score indicated high stress.^[41,42] This study revealed progressive improvement in mental stress levels related to IBS symptoms from baseline to weeks 4, 8, and 12. These outcomes corroborate those of Majeed et al,^[43] who reported significant alleviation of major depressive disorder and IBS symptoms in 40 patients treated with B. coagulans MTCC 5856.

Safety assessment revealed an encouraging profile, as no fatalities or SAE were documented throughout the study. At the end of the trial, all blood parameters were within normal limits, which demonstrates the overall safety and tolerability of B. coagulans BCP92.

The results presented herein provide a comprehensive and detailed analysis of the efficacy and safety of B. coagulans BCP92 therapy in IBS management. Interrelated multidimensional assessments ranging from symptom severity to mental well-being to stool consistency and inflammatory markers help to understand the differences in treatment across various dimensions among patients. Strict adherence to the protocols during the study design period increased the generalizability and reliability afforded by its robustness.

B. coagulans BCP92 has emerged as a promising therapy for IBS, demonstrating significant efficacy in alleviating symptoms, enhancing stool consistency, and promoting improved mental well-being. It is genetically stable.^[44] Also, it is GRAS approved strain by United State Food and Drung Administration (GRN1159, https://www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=GRASNotices&id=1159). These findings are supported by 2 key observations: a lack of any considerable adverse reactions toward it and its safe mode of action. The only limitation of the trial is limitation of trial is it is done on only Indian participants so worldwide data are not available. However, this can be addressed in the next phase by planning for more diverse study group.

This multidimensional approach to IBS management sets a new standard for future research by advocating a comprehensive evaluation beyond symptomatology to consider broader issues affecting patients’ overall lives. This study offers insights into B. coagulans BCP92 as well as a larger dialogue on the integrative evaluation of treatments in conditions that are complex and multifaceted.

5. Conclusion

The present extensive study has shown that B. coagulans BCP92 (Heyndrickxia coagulans), a probiotic strain, is effective in treating IBS. Multifaceted analysis, which includes aspects such as demographics, symptom severity, global symptom improvement, GI symptom frequency, stool consistency, and inflammatory markers as well as mental stress reduction and anxiety levels, has provided a clear picture of the effects of the intervention on IBS from various dimensions. The internal validity of this study was strengthened by the demographic diversity of participants drawn from different backgrounds, without any dropouts or protocol deviations, to enhance the generalization of the findings.

Overall, the safety evaluation, including dosage compliance, adverse events, and clinical laboratory parameters, confirmed that B. coagulans BCP92 had a good safety profile. The absence of SAE or treatment-emergent adverse events, along with the mildness of reported adverse events, indicated that the intervention was acceptable. Finally, it can be concluded that B. coagulans BCP92 is an encouraging therapeutic strategy for IBS, as it improves stool consistency and mental well-being.

Author contributions

Conceptualization: Sohel S. Shaikh.

Data curation: Sohel S. Shaikh.

Formal analysis: Sohel S. Shaikh, Sanjay Kumar.

Project administration: Sohel S. Shaikh, Sanjay Kumar.

Supervision: Sohel S. Shaikh, Sanjay Kumar.

Writing – original draft: Sohel S. Shaikh.

Writing – review & editing: Sohel S. Shaikh, Sanjay Kumar.

Investigation: Sanjay Kumar.