Published online Jun 7, 2026. doi: 10.3748/wjg.v32.i21.117959
Revised: January 28, 2026
Accepted: February 28, 2026
Published online: June 7, 2026
Processing time: 157 Days and 15.7 Hours
The global prevalence of functional constipation is approximately 12%. It is cha
To investigate whether L. plantarum improves constipation and QoL in healthy subjects experiencing occasional constipation.
The effect of L. plantarum was studied in a randomized, double-blind, placebo-controlled, parallel clinical trial carried out at one site in London, Canada, and included 100 healthy subjects with occasional constipation. Following a 2-week run-in period, subjects were randomized to consume either L. plantarum or placebo (1:1) for an 8-week period. Between-group differences in gut transit time, number of CSBM, stool consistency (Bristol Stool Scale), frequency of flatulence, and QoL were eva
The L. plantarum group (n = 49) showed significant improvements in stool consistency (0.91 ± 1.04 L. plantarum vs 0.43 ± 1.15 placebo, P = 0.023) and percentage of CSBM without hard or lumpy stools (30.2 ± 38.8 vs 11.9 ± 34.8, P = 0.005) compared to placebo (n = 48) after 8 weeks (per-protocol population). Significant improvements in flatulence (-0.26 ± 0.59 vs -0.06 ± 0.53, P = 0.043), and QoL in the satisfaction domain (-1.15 ± 1.09 vs -0.76 ± 1.16, P = 0.007) were also seen in the L. plantarum group compared to placebo. A post hoc analysis of 77 subjects with ≤ 3 weekly bowel movements (BMs) at baseline showed a significantly greater increase in weekly CSBM for the L. plantarum group compared to placebo (3.0 ± 3.0 vs 1.8 ± 2.4, P = 0.024).
Supplementation of L. plantarum (Lp299v and LpGOS42) for eight weeks significantly increases the number of BM, improves the stool consistency, reduces flatulence and improves QoL in subjects with occasional constipation.
Core Tip: The strain Lactiplantibacillus plantarum (L. plantarum) 299v (Lp299v) has previously been shown to have positive effects on irritable bowel syndrome. For the first time, a randomized, double-blind, placebo-controlled study has evaluated the effects of Lp299v, together with a small amount of a secondary strain (L. plantarum GOS42), on constipation in otherwise healthy subjects. Supplementation of these two probiotic strains for eight weeks had a significant positive effect compared to placebo on various constipation-related symptoms such as number of weekly bowel movements (BMs), stool consistency, percentage of stools with hard/lumpy consistency, flatulence, and satisfaction with BM regularity.
- Citation: Önning G, Vegge CS, Montelius C, Lewis ED, Al-Wahsh H, Moulin M, Crowley DC, Guthrie N. Effects of Lactiplantibacillus plantarum 299v and Lactiplantibacillus plantarum GOS42 on gastrointestinal symptoms in healthy adults with occasional constipation. World J Gastroenterol 2026; 32(21): 117959
- URL: https://www.wjgnet.com/1007-9327/full/v32/i21/117959.htm
- DOI: https://dx.doi.org/10.3748/wjg.v32.i21.117959
The global prevalence of functional constipation (FC) is about 12% and is more commonly reported in women (15%) than men (8%)[1]. FC is characterized by low number of weekly bowel movements (BMs), lumpy or hard stools, straining, incomplete evacuation, and anorectal obstruction. FC often impacts quality of life (QoL) and may lead individuals to seek medical attention. Studies indicate that constipation can have wider consequences, including negatively affecting liver and kidney function and contributing to chronic age-related diseases[2]. One potential mechanism for this may be changes in the gut microbiota composition during constipation with a switch from saccharolytic fermentation toward proteolytic fermentation and hence decreased production of beneficial short-chain fatty acids (SCFAs)[2].
The exact mechanism behind constipation is unclear but may involve visceral hypersensitivity, abnormalities in sensory/motor function, delayed colonic transit, and altered central perception[3]. To manage constipation, recommendations typically consist of lifestyle modifications including increased fluid intake, dietary fiber intake, and physical activity. Pharmacological therapies are also available and include laxatives, secretagogues, and 5HT4 agonists. However, these may lead to adverse effects such as diarrhea and dependency. There is, therefore, a need for more tolerable solutions to manage constipation.
Probiotics can have a positive effect on constipation, as documented in several meta-analyses[4-6]. Dimidi et al[4] included 14 studies in their meta-analysis and concluded that probiotics, especially Bifidobacterium lactis (B. lactis) strains, have beneficial effects on whole-gut transit time, stool frequency, and stool consistency in constipated subjects. Zhang et al[6] included 15 studies in their meta-analysis and had similar findings but concluded that multispecies probiotics were most efficient to relieve constipation. The most recent meta-analysis by Ding et al[5] evaluated both synbiotics (six studies) and probiotics (11 studies) and concluded that synbiotics and multispecies probiotics were the best formulations to improve constipation. Large heterogeneity is observed among the included studies due to differences in doses used, intervention lengths, and format/formulation (in food vs food supplement). Furthermore, most of the studies were small, with fewer than 100 subjects. Five studies with Lactiplantibacillus plantarum (L. plantarum) were included in the meta-analyses, of which four featured L. plantarum in combination with other probiotic strains, while only one short study (seven days) tested L. plantarum intervention alone.
One of the most clinically investigated L. plantarum strains is L. plantarum 299v (Lp299v; DSM9843, LP299V®)[7]. Studies with Lp299v have shown positive effects on gastrointestinal health, particularly in individuals with irritable bowel syndrome (IBS)[8-10]. After four weeks’ supplementation of Lp299v, overall IBS symptoms and abdominal pain were significantly reduced and a significant positive effect on flatulence and bloating were observed compared to placebo[8-10]. In the Niedzielin et al[9] study involving subjects with IBS, 50% of subjects in the intervention group reported constipation at baseline; this figure dropped to 20% after four weeks of Lp299v supplementation. Corresponding figures for the placebo group were 55% at baseline and 45% after four weeks (P = 0.17 between groups), indicating that Lp299v may have a positive effect on constipation. The aim of the present study was to investigate the effect on Lp299v in combination with a lower amount of another L. plantarum strain [L. plantarum GOS42 (LpGOS42); the combination hereafter referred to as L. plantarum] on constipation in subjects experiencing occasional constipation but not diagnosed with IBS. The LpGOS42 strain was added due to its complimentary anti-inflammatory properties (unpublished data). Occasional constipation is a milder form of FC. There is no consensus on its precise diagnostic criteria, but publications have highlighted the need for a formal definition since it is a common problem[11]. Recently, a Rome foundation working group suggested occasional constipation be defined as “the presence of at least one FC symptom, in the absence of alarming signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management”[12]. Stricter criteria for occasional constipation were used in the present study since the definition mainly is intended to be used to diagnose occasional constipation. The criteria were based on the Rome IV criteria for FC, which is recommended for clinical trials, but the subjects did not have chronic constipation.
The primary endpoint of this study was the effect of L. plantarum on gut transit time using a blue dye method[13]. There are other methods to analyze gut transit including using radio-opaque markers, colonic scintigraphy, or wireless mobility capsules. These methods are of high quality, but they require in-person visits, equipment, and staff. This has led to the development of the blue dye method, a simpler testing method that can be performed at home[13]. With this method, gut transit time is measured by instructing subjects to consume a blue dyed muffin and recording the time from consumption until a blue color appears in the feces. This method has been used to characterize gut transit time in a healthy population (n = 866) and identify possible links to differences in the microbiota composition[13]. Secondary endpoints followed in this study included the number of weekly BM, stool consistency, gastrointestinal function, bloating, flatulence and constipation related QoL.
This study was a randomized, double-blind, placebo-controlled, parallel-designed study carried out at a single site at KGK Science, London, Canada, between June 2024 and December 2024. The study period consisted of a screening visit followed by a 2-week run-in phase, and an 8-week intervention phase, with visits at baseline (day 0, eligible subjects were randomized), day 28 (week 4), and day 56 (week 8).
Before any study-related procedures, all subjects gave written informed consent, which specifically indicated that participation was voluntary and could be terminated at any time without giving any reason. The study was approved by the Natural and Non-prescription Health Products Directorate, Health Canada on January 31, 2024. Ethical approval was granted on May 15, 2024, by the Institutional Review Board Services (Advarra, Aurora, Ontario, Canada; Approval No. Pro00079027). The study was conducted in accordance with the ethical principles in the Declaration of Helsinki, the International Council for Harmonization and E6 R2 Guideline for Good Clinical Practice and was registered with Clinicaltrials.gov (NCT06444139) before the first subject was enrolled.
Healthy women and men between the ages of 18 years and 65 years were recruited via an internal database, digital marketing ad campaigns, and local general marketing campaigns. To be included, the subjects must have reported occasional constipation that was assessed at screening and confirmed at baseline and defined as either (1) or (2) or (3): (1) ≤ 5 complete spontaneous BM (CSBM) per week and either one of the following: At least 25% of BM are Bristol Stool Scale (BSS) type 1 or 2 or straining for most of the BM (≥ 50%), defined as 3 minutes or more during BM; (2) At least 50% of BM are BSS type 1 and 2; and (3) ≤ 3 CSBM per week. Subjects were excluded if they had allergy, sensitivity, or intolerance to study products or clinical assessment materials, chronic constipation, current or history of significant diseases or abnormalities of the gastrointestinal tract, unstable metabolic disease or chronic diseases, history of or current diagnosis with kidney and/or liver diseases, chronic use of cannabinoid products, alcohol or tobacco products, use of over-the-counter medications or supplements (probiotics, prebiotics, synbiotics, laxatives), or intake of antibiotics that could affect gastrointestinal symptoms. Subjects agreed to maintain their current lifestyle habits (diet, physical activity, medications, supplements and sleep) as much as possible throughout the study. They also had to note any changes in habits in the study diary. To evaluate if there were any dietary changes over time, subjects completed 3-day food records in the week prior to the visit at baseline, week 4, and week 8 (Libro, Nutritics).
The subjects were randomly assigned to one of two treatment arms: L. plantarum or placebo (1:1). The randomization list was computer-generated using Greenlight Guru Clinical (Greenlight Guru, IN, United States). The L. plantarum arm received one capsule daily containing 1010 colony forming unit (CFU) Lp299v, 109 CFU LpGOS42, maize starch, mal
The primary endpoint of the study was difference in gut transit time between the L. plantarum and placebo groups, while secondary endpoints were number of CSBM, stool consistency, gastrointestinal symptoms, bloating, flatulence and QoL.
Gut transit time: The gut transit time was evaluated three times: Seven days prior to baseline visit, at week 4, and at the week 8 visit. Subjects were instructed to consume a standardized breakfast within a 60 ± 30 minutes window prior to consuming two muffins containing the blue dye[13]. For the standardized breakfast, subjects had two options (each providing 260 kcal): Either one egg and one slice of toast with one tablespoon of preferred cooking oil or half a cup of yogurt and one slice of toast with one tablespoon of spread. They were instructed to consume the same breakfast at each timepoint. The blue muffins were to be consumed within a 10 ± 5 minutes window. Subjects were instructed to refrain from consuming caffeine and/or caffeinated drinks in the morning and not to consume other food or drinks (water allowed) for four hours after blue muffin consumption. Subjects were instructed to log the first appearance of blue color in their stool in their study diary. Gut transit time for each subject was measured from the time of muffin consumption to the first visualization of blue color within their stool.
BMs and stool consistency: CSBM were assessed daily and noted in the study diary together with stool consistency. A BM was considered complete and spontaneous if: (1) The subject did not report use of laxatives, enemas, or suppositories during the 24 hours prior to the BM; and (2) The subject had a feeling of complete defecation. The BSS was used to eva
Bloating and flatulence: The frequency of bloating and flatulence was assessed daily and noted in the study diary. The Likert scale ratings were: 1 (less than usual), 2 (as much as usual), 3 (somewhat more than usual), and 4 (much more than usual). The frequency of bloating and flatulence in the week before the visit at baseline, week 4, and week 8 was calculated by finding the mean value of the measurements.
Gastrointestinal Symptom Rating Scale: The Gastrointestinal Symptom Rating Scale (GSRS) is a validated 15-item scale that evaluates the current severity of common gastrointestinal symptoms[14]. A modified GSRS was used in the study, which consisted of 14 items on a four-point scale from 0 (no symptoms) to 3 (severe symptoms). GSRS has five subscales: Abdominal pain, reflux syndrome, diarrhea syndrome, indigestion syndrome, and constipation syndrome. The modified GSRS was administered at all visits (baseline, week 4, and week 8).
Patient Assessment of Constipation Quality of Life: The Patient Assessment of Constipation Quality of Life (PAC-QoL) is a standardized questionnaire that evaluates patient-reported constipation over time. It consists of 28 items with an overall score and four subscales (worries and concerns, physical discomfort, psychosocial discomfort, and satisfaction)[15]. The subjects evaluated their symptoms for the prior two weeks on a scale from 0 (not at all) to 4 (extreme). The PAC-QoL was administered at baseline, week 4, and week 8. Data related to satisfaction is presented as a reverse score and thus a lower score represents higher satisfaction.
Safety: The subjects recorded adverse events (AEs) in the daily study diary and were also asked at each visit if they experienced any AE since the previous visit. Blood samples were taken to detect any change in liver function, kidney function, or blood glucose metabolites. Various hematology parameters were assessed and analyzed with Dynacare using standardized procedures. Blood pressure and heart rate were checked at every visit.
The sample size was calculated based on the change in gut transit time previously reported, with standard deviations of 31.65 hours for the L. plantarum group and 19.32 hours for the placebo group[16]. Assuming a two-sided significance level of 0.05 and a difference in change from baseline at week 8 in gut transit time between L. plantarum and placebo groups of 19.3 hours, 40 subjects were required in each treatment group (80 total) to achieve 90% power. A total of 100 subjects, with 50 subjects in each treatment group, were required to allow for an attrition rate of 20%. Sample size calculations were performed using t-test for two independent samples in G*Power software, version 3.1.9.6.
The difference in change between the study arms (L. plantarum vs placebo) for each outcome was analyzed using linear mixed models. These models included the following fixed effects: Study group, visit (timepoint), the interaction between group and visit, and the baseline measurement. Subject ID was included as a random effect to account for repeated measures within individuals. The dependent variable in each model was the outcome of interest. Prior to analysis, outcome variables were assessed for normality using the Shapiro-Wilk test and Q-Q plots. To compare the two study arms at each timepoint, two-sample t-tests were conducted. Paired t-tests were used to evaluate changes within each study arm relative to baseline. For categorical variables, Fisher’s exact test was employed to compare distributions between the study arms. All analyses were two-sided at a 5% significance level and were performed using the R Statistical Software Packaging version 4.3.2. The statistical review of the study was performed by a biomedical statistician.
The intention-to-treat (ITT) population included all randomized subjects with at least one reported consumption of any of the products. The per-protocol (PP) population included all randomized subjects with complete data for the primary outcome and minimum 80% reported compliance in terms of amount of product consumed with no major protocol deviations. All subjects who have taken at least one dose of the study product were included in the safety population. The results presented in this paper are for the PP population if not otherwise indicated.
Two hundred and twelve subjects were screened for eligibility, and of these 102 did not meet either the inclusion or exclusion criteria, while 10 subjects were excluded for other reasons (Figure 1). One hundred subjects were randomized into the study, 50 subjects per group. For both groups all subjects finished the study and were included in the ITT population. The PP population consisted of 97 subjects: 49 subjects in the
The reasons for exclusion from the PP population included delay of the last visit by more than one week (one subject in each group) and coronavirus disease 2019 infection at the time when the primary variable should be assessed (one subject in the placebo group).
The PP population had a mean age of 44 (range 19-66) years, the mean body mass index was 28 kg/m2, and 78% of the subjects were women (Table 1, no significant difference between groups).
| ITT L. plantarum (n = 50) | ITT placebo (n = 50) | PP L. plantarum (n = 49) | PP placebo (n = 48) | |
| Women | 38 (76) | 40 (80) | 37 (76) | 38 (79) |
| Age (year) | 44.3 ± 13.3 | 43.8 ± 11.9 | 44.0 ± 13.3 | 43.9 ± 12.1 |
| BMI (kg/m2) | 28.4 ± 7.9 | 27.8 ± 6.1 | 28.5 ± 7.9 | 28.0 ± 6.1 |
| Fiber intake (g/day) | 16.4 ± 8.2 | 14.4 ± 6.2 | 16.4 ± 8.2 | 14.2 ± 6.2 |
| Exercise regularly | 31 (62) | 31 (62) | 30 (61) | 29 (60) |
Based on 3-day food records, dietary fiber intake among subjects was 14-16 g/day at baseline (Table 1) with no change over time or differences between the groups. There was also no difference between the groups for intake of macronutrients (protein, fat, carbohydrates) at any timepoint. Approximately 60% of the subjects in each group exercised regularly at baseline (Table 1).
Compliance was excellent in the PP population; the mean intake of L. plantarum product was 99.9% (94.9-105.4) while the mean intake was 99.3% (94.6-105.4) for the placebo product during the 8-week intervention period.
Fifty-one post-emergent AEs were reported in the safety population (n = 100), with 33 subjects experiencing these events. All reported AEs were classified as “mild” or “moderate”. There were 21 AEs reported by subjects in the L. plantarum group and 30 AEs reported in the placebo group. One mild AE (headache) was classified as “possibly” related to the study product in the L. plantarum group, which lasted four days. All AEs were resolved by the end of the study period or upon subsequent follow up. Hematology and clinical chemistry values found to be outside the normal laboratory range were deemed not clinically relevant, and there were no AEs related to the measured vital signs (blood pressure, heart rate). Thus, intake of L. plantarum was found to be safe and well tolerated.
The mean (range) gut transit time measured using the blue dye method at baseline was 39.8 (3-145) hours and 48.8 (6-143) hours in the L. plantarum and placebo groups, respectively (no significant difference; Table 2). No significant changes in gut transit time were observed after 4- or 8-weeks’ intervention in any of the groups. At the end of treatment, the mean change (range) was +0.4 (-71 to 57) hours in the L. plantarum group and -3.4 (-117 to 96) hours in the placebo group (P = 0.98 between groups).
| Baseline | 4 weeks | 8 weeks | Change baseline-week 4 | Change baseline-week 8 | P value, between week 81 | |
| Transit time (hour) | ||||||
| L. plantarum | 39.8 ± 29.2 | 41.8 ± 33.75 | 40.2 ± 27.1 | 1.9 ± 23.9 | 0.4 ± 23.0 | |
| Placebo | 48.8 ± 31.9 | 45.3 ± 26.75 | 45.4 ± 27.0 | -3.4 ± 26.4 | -3.4 ± 32.5 | 0.980 |
| CSBM per week | ||||||
| L. plantarum | 2.6 ± 2.2 | 4.0 ± 3.3 | 5.0 ± 3.0 | 1.4 ± 3.0b | 2.4 ± 3.2c | |
| Placebo | 1.7 ± 1.8 | 3.1 ± 3.4 | 3.6 ± 3.1 | 1.4 ± 3.0b | 1.9 ± 2.7c | 0.182 |
| Stool consistency2 | ||||||
| L. plantarum | 2.54 ± 0.73 | 3.11 ± 1.03 | 3.44 ± 1.01 | 0.58 ± 1.13b | 0.91 ± 1.04c | |
| Placebo | 2.62 ± 0.98 | 2.97 ± 1.01 | 3.06 ± 1.05 | 0.35 ± 0.95a | 0.43 ± 1.15a | 0.023 |
| BM without hard/lumpy stools (%) | ||||||
| L. plantarum | 50.5 ± 33.8 | 67.5 ± 32.2 | 80.7 ± 29.7 | 17.0 ± 39.7c | 30.2 ± 38.8c | |
| Placebo | 58.7 ± 34.2 | 65.1 ± 34.2 | 70.5 ± 33.3 | 6.4 ± 32.6c | 11.9 ± 34.8c | 0.005 |
| Bloating frequency3 | ||||||
| L. plantarum | 2.07 ± 0.42 | 1.98 ± 0.56 | 1.84 ± 0.55 | -0.10 ± 0.58 | -0.23 ± 0.56b | |
| Placebo | 2.05 ± 0.40 | 1.93 ± 0.52 | 1.90 ± 0.61 | -0.12 ± 0.40a | -0.15 ± 0.50a | 0.473 |
| Flatulence frequency3 | ||||||
| L. plantarum | 2.01 ± 0.43 | 1.85 ± 0.51 | 1.75 ± 0.55 | -0.16 ± 0.53a | -0.26 ± 0.59b | |
| Placebo | 2.04 ± 0.41 | 1.98 ± 0.60 | 1.98 ± 0.67 | -0.06 ± 0.44 | -0.06 ± 0.53 | 0.043 |
| GSRS total score | ||||||
| L. plantarum | 0.69 ± 0.28 | 0.58 ± 0.27 | 0.53 ± 0.28 | -0.12 ± 0.20 c | -0.16 ± 0.28 c | |
| Placebo | 0.68 ± 0.28 | 0.54 ± 0.20 | 0.53 ± 0.24 | -0.14 ± 0.28b | -0.15 ± 0.27 c | 0.934 |
| GSRS constipation | ||||||
| L. plantarum | 1.56 ± 0.49 | 1.19 ± 0.55 | 1.01 ± 0.59 | -0.37 ± 0.54 c | -0.55 ± 0.57 c | |
| Placebo | 1.60 ± 0.55 | 1.26 ± 0.62 | 1.24 ± 0.64 | -0.34 ± 0.78b | -0.36 ± 0.71b | 0.073 |
| Constipation QoL total score | ||||||
| L. plantarum | 1.48 ± 0.65 | 1.11 ± 0.61 | 0.90 ± 0.70 | -0.35 ± 0.54c | -0.57 ± 0.70c | |
| Placebo | 1.59 ± 0.66 | 1.21 ± 0.62 | 1.09 ± 0.61 | -0.38 ± 0.56c | -0.51 ± 0.62c | 0.314 |
| Constipation QoL satisfaction4 | ||||||
| L. plantarum | 2.88 ± 0.73 | 2.16 ± 0.74 | 1.74 ± 1.04 | -0.70 ± 0.84c | -1.15 ± 1.09c | |
| Placebo | 3.04 ± 0.67 | 2.52 ± 0.75 | 2.28 ± 1.00 | -0.52 ± 0.74c | -0.76 ± 1.16c | 0.007 |
The mean ± SD of weekly CSBM was higher at baseline in the L. plantarum group (2.6 ± 2.2) compared to the placebo group (1.7 ± 1.8; P = 0.031 between groups; Table 2). The number of CSBM increased significantly over time in both groups, with no significant difference between L. plantarum and placebo groups at week 4 (1.4 ± 3.0 vs 1.4 ± 3.0) or week 8 (2.4 ± 3.2 vs 1.9 ± 2.7). At the same time, the stool consistency score (BSS) significantly increased, indicating softer stools (Table 2 and Figure 2). The BSS score was similar in both groups at baseline and increased significantly in both groups from baseline to week 4 and week 8. However, the increase in BSS score was significantly higher in the L. plantarum group compared to the placebo group at week 8 (0.9 ± 1.0 vs 0.4 ± 1.1, P = 0.023, linear mixed model analysis).
The mean weekly percentage of BM without hard/lumpy stools was 50% at baseline in the L. plantarum group and 59% in the placebo group (no significant difference; Table 2). By week 8, the mean weekly value of BM without hard/lumpy stools had reached 81% in the L. plantarum group, which was a significantly greater increase compared to the placebo group where the corresponding figure was 70% (P = 0.005 between groups, logistic generalized linear mixed model analysis).
At baseline, 80% of subjects reported having three or fewer CSBM per week. A post hoc analysis was conducted for this subgroup to assess changes in the number of weekly CSBM over time (Table 3). In this subgroup, the mean ± SD number of weekly CSBM increased significantly by 3.0 ± 3.0 in the L. plantarum group, compared to an increase of only 1.8 ± 2.4 in the placebo group in week 8 (Figure 3; P = 0.024 between groups, linear mixed model analysis).
| ITT L. plantarum | ITT placebo | P value, between groups | PP L. plantarum | PP placebo | P value, between groups | |
| Baseline | 1.6 ± 1.2 | 1.2 ± 1.2 | 0.1381 | 1.6 ± 1.2 | 1.2 ± 1.2 | 0.1411 |
| Week 4 | 3.3 ± 3.0 | 2.5 ± 2.3 | 0.2121 | 3.3 ± 3.0 | 2.3 ± 2.1 | 0.1391 |
| Week 8 | 4.5 ± 3.0 | 3.1 ± 2.5 | 0.0281 | 4.6 ± 3.0 | 3.0 ± 2.5 | 0.0151 |
| Change baseline-week 4 | 1.7 ± 3.1a | 1.3 ± 2.1b | 0.3562 | 1.7 ± 3.2a | 1.2 ± 2.0b | 0.2442 |
| Change baseline-week 8 | 2.9 ± 3.0b | 1.9 ± 2.4b | 0.0482 | 3.0 ± 3.0b | 1.8 ± 2.4b | 0.0242 |
The frequency of bloating decreased significantly over time in both groups but no difference between the groups was observed. However, the frequency of flatulence decreased significantly in the L. plantarum group only, over time. By week 8, the frequency of flatulence in the L. plantarum group was significantly lower compared to the placebo group (P = 0.043 between groups, linear mixed model analysis; Table 2).
The gastrointestinal function was evaluated using the GSRS (Table 2). In general, the subjects displayed low scores with total mean GSRS score of 0.69 at baseline and 0.53 at the end of the study in both groups (Table 2). However, the constipation subscale mean score was over 1 (more than occasional problems). The constipation subscale includes questions about hard stools, decreased passage of stools, and feelings of incomplete evacuation. The mean constipation subscale score was 1.6 at baseline in both groups and decreased significantly over time to a mean ± SD of 1.01 ± 0.59 in the L. plantarum group and 1.24 ± 0.64 in the placebo group by week 8 (P = 0.073 between groups, linear mixed model analysis; Table 2).
QoL was evaluated using the PAC-QoL questionnaire. The total score decreased over time in both groups, showing a significant improvement in overall QoL during the 8 weeks, with no difference between the groups (Table 2). The highest score detected among the four subscales was for satisfaction. The mean score was 2.88 and 3.04 at baseline in the L. plantarum and placebo group, respectively. The satisfaction score improved significantly over time in the L. plantarum group compared to placebo; by week 8, the L. plantarum group had a mean ± SD of 1.74 ± 1.04 compared to the placebo group that had a score of 2.28 ± 1.00 (P = 0.007, linear mixed model analysis). This indicates that the subjects in the L. plantarum group were more satisfied with how often they had a BM and with the regularity of the BM compared to the placebo group.
The present study was conducted to gain insight into the effect of two probiotic strains, Lp299v and LpGOS42 (L. plantarum), on occasional constipation. The findings showed that L. plantarum had a significant positive impact on many of the symptoms that are associated with constipation such as number of weekly BM, stool consistency, percentage of stools with hard/lumpy consistency, flatulence, and satisfaction with BM regularity.
The subjects in the present study were healthy besides having occasional constipation. This was supported by the results from the GSRS questionnaire, where the subjects reported low scores across most domains except for the constipation domain. The subjects also did not have constipation-predominant IBS (IBS-C) according to the GSRS questionnaire, since recurrent abdominal pain was not present (at baseline 91% had no/brief abdominal pain and 9% had occasional pain). One earlier study on probiotics has been published that used similar inclusion criteria for occasional constipation as in the present study[17]. The subjects were older (50-85 years) and the number of weekly BM was higher at baseline than in the present study (about 6 compared to 2.2), while the stool consistency was similar. Thus, despite using the same inclusion criteria, the number of weekly BM differed; this is likely related to the fact that the inclusion was based on several criteria. This phenomenon has also been observed for studies that include subjects based on the Rome criteria for FC[18].
Gut transit time has previously been measured in probiotic studies on constipated subjects using radio-opaque markers[16,18-20] showing a significant effect in a meta-analysis where supplementation of probiotics reduced the gut transit time by 12.4 hours[4]. To avoid radiation exposure and use a simpler method, a blue dye method was applied in the present study to measure the gut transit time[13]. The detection of the blue dye worked well in the sense that only two subjects failed to observe a blue color in the feces (0.7% of the transit measurements). However, no significant change in the gut transit time was observed, while other transit related endpoints were significantly changed (number of BM, stool consistency). The absence of results on gut transit time is likely due to the lack of guidance to the subjects on when to consume the blue dye muffin in relation to their last BM. This is supported by the substantial variation in baseline gut transit time observed, ranging from 3 hours to 145 hours. This factor made it difficult to observe a significant effect on the change in transit time over time and between groups. In an earlier study the blue dye method was applied in a large non-intervention study involving healthy subjects[13]. The gut transit time was positively associated with the number of BM and negatively associated with the stool consistency. Most of the subjects in the study had a high BM frequency (≥ 7 BM per week, 67% of the subjects)[13]. This method may more accurately measure the gut transit time for these subjects with frequent BM compared to subjects that have much less BM as in the present study.
The blue dye method has, to date, only been used in a few intervention studies[21-23]. Mysonhimer et al[23] used a modified technique to estimate the gut transit time, where healthy subjects were given three capsules containing powdered blue dye and instructed to consume one capsule following each of three consecutive BM, after which an average gut transit time was calculated for each subject. This modified blue dye approach corrected for latest BM and could be a more suitable method to obtain more accurate gut transit time for constipated subjects in future studies.
The number of CSBMs increased significantly over time in both groups. By week 8, no statistically significant difference was observed between the groups; however, the mean increase was larger in the L. plantarum group compared to the placebo group (2.4 vs 1.9 weekly CSBM, respectively). In a post hoc subgroup analysis involving subjects with more severe constipation (≤ 3 weekly CSBM at baseline, 80% of the study population), a significant between-group difference was detected. The L. plantarum group reported a mean of 4.6 weekly CSBM, an increase of 3.0 from baseline, corresponding to a difference of +1.1 weekly CSBM compared to placebo at week 8 (Figure 3). This finding is consistent with previous meta-analyses on FC, which reported probiotic-associated increases in BM frequency ranging from +0.93 to +1.3 CSBM relative to placebo[4-6]. The observed effect on BM in the present trial also supports earlier findings for other L. plantarum strains[17,24,25] reinforcing the potential of this species in alleviating symptoms of constipation. In a study by Singh et al[17] supplementation of two L. plantarum strains (KABP031, KABP032, ≥ 1 × 109 CFU/day) significantly increased the number of BM compared to placebo after 1.5-month intervention but not after three months in older subjects with occasional constipation. Supplementation of a high dose of one L. plantarum strain [L. plantarum P9 (LpP9), 2 × 1011 CFU/day] for four weeks by subjects with FC increased the weekly CSBM to 3.1 in the L. plantarum group and to 2.4 in the placebo group (P = 0.039 between groups)[24]. A 7-day intervention trial in subjects with FC also saw a sig
The increase in the number of weekly BM was accompanied by a corresponding change in the BSS score towards loose stools. At week 8 of the intervention, the change in stool form was significantly larger in the L. plantarum group, with a mean increase of 0.5 compared to the placebo group. The shift from harder to looser stools aligns with previous findings from probiotic treatments[4-6] and demonstrates that the probiotic combination of Lp299v and LpGOS42 effectively addresses the most challenging aspects of constipation, namely BM frequency and stool consistency.
Flatulence is commonly associated with constipation and can pose a significant social concern for affected individuals. Following eight weeks’ treatment, the flatulence frequency was significantly lower in the L. plantarum group compared to the placebo group. These findings on subjects with occasional constipation align with previous research showing that a daily dose of 1010 CFU Lp299v can significantly reduce flatulence in individuals with IBS[10] and in healthy individuals[27].
An earlier study with Lp299v on subjects with IBS showed that in a subgroup with constipation (IBS-C, n = 47), the IBS symptom severity scale (IBS-SSS) was significantly improved in the Lp299v treated group compared to placebo[28]. The IBS-SSS score was primarily improved with respect to satisfaction with bowel habits and how IBS affects and interferes with life in general[29] for the Lp299v subgroup with IBS-C. These previous findings correlate quite well with the results in the present trial, where a significant positive effect on the QoL satisfaction item in PAC-QoL was observed. The PAC-QoL questionnaire has been included in previous constipation studies investigating probiotics; however, no effect on satisfaction in PAC-QoL was observed using LpP9[24] or B. lactis HN019[18,30], while supplementation of Bifidobacterium longum CCFM1112 significantly improved the total PAC-QoL score[31]. The difference in the results among studies shows that it is important to perform strain-specific studies to evaluate the effect on constipation and QoL.
According to a review of clinical trials on chronic constipation, the placebo response is typically high, ranging from 4% to 44%, depending on the endpoint[32]. High placebo responses exist for example for self-reported measurements like flatulence and QoL questionnaires. One factor that also influences the placebo response is the length of the trial, since it often becomes weaker over time[33], and this was also observed in the present study. For example, in week 4 the mean number of weekly CSBM increased to 1.4 for both groups, while in week 8 the mean number of weekly CSBM increased more in the L. plantarum group (2.4 vs 1.9 in the placebo group). Placebo responses were also observed for other en
From earlier studies it is known that Lp299v survives the passage through the intestine and can be found in biopsies taken in the upper jejunum, colon and rectum[7]. Moreover, Lp299v has an ability to adhere to the gut epithelium with a mannose-binding mechanism and to the mucus layer with electrostatic and hydrophobic interactions[7]. Lp299v has therefore a clear potential to modulate key mechanisms governing colonic motility. Microbiota-derived or microbiota-modulated compounds known to influence colonic motility include bile acids, SCFAs, methane, and tryptophan metabolites[34,35]. Thus, there may be multiple mechanisms responsible for the effects seen on constipation in the present study, since these compounds influence many physiological functions including those within the immune and nervous systems[34,35]. Lp299v has in previous clinical studies been shown to increase the microbiota diversity, increase the fecal carboxylic acid concentration, and affect the immune system[7]. Another mechanism for the supportive effects of Lp299v and LpGOS42 on constipation, can be an effect on the enteric nervous system (ENS) that plays a critical role in the regulation of gastrointestinal motility and is a key factor in the pathophysiology of constipation. The effects on the ENS in relation to constipation have previously been studied with another L. plantarum strain, L. plantarum HEAL9 (LpHEAL9)[36]. The LpHEAL9 strain was administered to SAMP8 mice that, due to the nature of the model, typically have a reduced fecal output compared to control SAMR1 mice[36]. Daily gavage of LpHEAL9 at a dose of 109 CFU over two months significantly increased the fecal output in SAMP8 mice relative to SAMP8 control mice. To further investigate this effect, ex vivo analyses of colonic motor pathways were conducted. These studies revealed that LpHEAL9 enhances colonic motility by modulating excitatory cholinergic pathways within the ENS, an essential route for peristaltic activity. A similar mechanism may also lie behind the effects seen in the present study, but further studies are needed to confirm this.
A key strength of the present study was the absence of dropouts, illustrating strong subject retention. Additionally, subject compliance was high, and only one AE was reported that was possibly related to the intake of L. plantarum, suggesting good tolerability of the intervention. Another notable strength was the monitoring of potential confounding factors, such as physical activity and dietary fiber intake, which enhances the reliability of the findings. This study has some limitations. One limitation is that the study was conducted at a single site in Canada. However, one of the included strains (Lp299v) has previously demonstrated gastrointestinal health benefits in diverse populations, including those in Sweden, Poland, and India[8-10]. An earlier study using Lp299v in subjects with IBS, showed beneficial effects on overall gastrointestinal function 12 months after the intervention had concluded[10]. For the present study it is difficult to know for how long the effects persisted and for future studies it should be valuable to include a follow-up period to evaluate this. As discussed above, a further limitation was that the gut transit measurement method was not optimized for subjects that had constipation, that made it difficult to evaluate the effect on the gut transit time. Previous research by Zhu et al[37] observed significant dysbiosis among subjects with FC that was linked to a reduction in the fecal microbiota richness and diversity compared to healthy subjects. Thus, including an analysis of the fecal microbiota could have provided further insights into how microbial composition and diversity play a role in the mechanisms underlying the observed effects in the present study. Another limitation was that although the study included 100 subjects, this sample size was insufficient to achieve statistical significance for certain endpoints. Future studies may therefore require a larger sample size to ensure adequate power to detect meaningful differences in these endpoints. Nevertheless, all gut health-related outcomes consistently indicated a clear beneficial effect of Lp299v and LpGOS42 on occasional constipation in healthy individuals.
In this study on healthy subjects with occasional constipation, supplementation of Lp299v and LpGOS42 (L. plantarum) for eight weeks significantly improved stool consistency, increased frequency of BM without hard/lumpy consistency, reduced frequency of flatulence, and improved satisfaction scores within QoL compared to placebo. In a subgroup with few BM at baseline, the number of weekly BM increased significantly more in the L. plantarum group compared to placebo. This demonstrates that supplementation of Lp299v and LpGOS42 can relieve many of the challenges that are linked to constipation.
The authors wish to thank Mary Farrell and Brandy Webb, Probi AB, for their scientific review of the manuscript. LP299V® is a trademarked and proprietary strain of Probi.
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