Safety and Exploratory Pre-Post Changes Associated with an Orally Disintegrating Three-Strain Probiotic Tablet in Older Adults with Functional Constipation: A Single-Center, Open-Label, Single-Arm Study.

Abstract

Background/objectives: Functional constipation is common in older adults and impairs quality of life. Evidence for multi-strain orally disintegrating (OD) probiotic formulations in this population remains limited.

Methods: In this single-center, open-label, single-arm pre-post study, adults aged 65-90 years meeting the Rome IV criteria for functional constipation were administered an OD tablet containing Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A for 8 weeks. The primary endpoint was change in the defecation score based on a modified Bristol Stool Form Scale. Secondary endpoints included stool frequency, straining, JPAC-QOL, the modified Constipation Scoring System, Izumo Scale, Dietary Variety Score (DVS), selected metabolic/nutritional variables, and exploratory gut microbiota analyses.

Results: Fifty participants provided consent, and 49 were included in the full analysis set; 45 participants completed the 8-week intervention and were included in the paired primary endpoint analysis. The defecation score showed a nominally significant change toward normalization of stool form at week 8 (IQR: -1.0, 7.0; 95%CI: -9.6, -4.2). Stool frequency did not change significantly, whereas constipation-related quality of life and symptom burden significantly changed. DVS increased modestly, and HbA1c decreased slightly; however, these secondary findings should be interpreted as exploratory because no adjustment for multiplicity was performed. Four patients withdrew from this study: one was due to death, but a causal relationship with the study drug was not confirmed. Two gastrointestinal adverse events could have been related to the study product. Exploratory subgroup analyses suggested a larger change in participants not receiving acid-suppressive therapy.

Conclusions: The three-strain OD probiotic tablet was associated with changes in stool form and constipation-related symptom burden in older adults with functional constipation. Because this was a single-arm, open-label study without multiplicity adjustment for secondary endpoints, the findings should be regarded as exploratory and hypothesis-generating. Given the absence of a control group, causal efficacy cannot be inferred, and placebo effects, natural symptom fluctuation, or other time-varying confounders cannot be excluded; therefore, the most robust conclusion is that the preparation appeared safe and well tolerated for over 8 weeks in this population.