Does the consumption of Probiotics enhance bowel habits in individuals with constipation? A systematic Review.

1. Abbreviations

RCT - Randomised Control Trial

NBD Neurological Bowel Dysfunction

PD Parkinson’s Disease

WHO World Health Organisation

NMS Non-Motor Symptom

SCF Short Chain Fatty Acid

PRISMA Preferred Reporting Items for Systematic Review and Meta – Analysis CFU Colony Forming Units

IBS Inflammatory Bowel Disease

FC Functional Constipation

CSS Constipation Scoring System

CTT Colon Transit Time

ANOSIM Analysis of Similarity

PAC_QoL Patient Assessment of Constipation – Quality of Life MTL Motilin

VIP Vaso-active Intestinal Polypeptide

ET1 Endothelin 1

GPX Glutathione Peroxidase

2. Abstract:

Background: The risk of gastrointestinal abnormalities especially constipation is increasingly observed in individuals with poor bowel habits and unbalanced nutrition intake. Constipation, though mainly not attributed to be as serious as other diseases, is now a common secondary symptom in various other health conditions, especially in people with neurodegenerative disorders. With a variety of probiotic products available in the market today, probiotics is increasingly used as a therapeutic alternative for constipation either knowingly or unknowingly. Also, constipation either directly or indirectly affects the quality of life and relatively reduces productivity in day to day to activities. It’s becoming a major cause for the deterioration of the social, mental, and physical well-being of an individual.

Objective: To provide an evidence-based systematic review on the consumption of probiotics and their associated benefits/risk in individuals with constipation, focusing on the efficacy of various probiotic strains available today.

Results: This systematic review included 9 Randomised Control Trials (RCTs) published in the last 5 years, conducted on 852 participants (adults with constipation). The review found that the use of probiotics could significantly alleviate constipation, but the outcome depends on the type of probiotic strain used. Several cultures of Lactobacillus, Bifidobacterium, and Bacillus depict promising results in treating constipation and related symptoms.

Conclusion: While the efficacy of probiotics in managing constipation is producing encouraging results, strain specific studies on large populations with or without other underlying health conditions need to be carried out for a better understanding of its interaction with the intestinal microbiome and to analyse any relative effects.

Keywords: Probiotics, Constipation, Adults, Bowel Habits, Rome Criteria, Probiotic Strains.

3. Introduction:

Constipation, defined as the difficult or rare passage of stool or both, is more common among the elderly than in younger age groups, which usually is attributed to a secondary cause of medicines, neurologic or systemic diseases[2]. Acute constipation might even result in the closure of the intestine which might lead to surgery [5]. Factors such as genetic predisposition, low fiber, and fluid consumption, hormonal imbalance, reduced mobility, the anatomical build of the body, side effects of medicine, and socio-economic status are triggers for constipation [5]. Notably, constipation has a significant correlation with obesity (Class II and III , Class II is defined by a Body Mass Index (BMI) of 35 to < 40 , Class III has a BMI of40 or higher ) and is posing a high challenge to the healthcare industry with the blooming increase in the obese population reaching 42% globally by 2025[6]. Constipation diagnoses in the UK account for more than 1 million GP consultations and 69054 hospital admissions annually [17].

Functional or chronic constipation has underlying multifactorial etio-pathological mechanisms. Although the disorder has no known structural abnormalities or infectious or metabolic causes, it still exhibits a significant healthcare burden with an estimated prevalence of 2.5% to 79% in adults [1] [3]. In addition to its clinical relevance, symptoms of constipation may get amplified by physiological, sociocultural, or intrapsychic factors which may contribute to reduced efficiency in professional life as well as in day-to-day activities [4]. Although various therapeutic algorithms are in place for treating constipation, lifestyle modifications, mainly dietary changes are the preferred first-line advice to tackle the condition. Adequate fiber supplementation and fluid intake are proven to be effective in improving stool frequency and transit time. Additionally, though patients opt for over-the-counter products to prescriptions medicines, behavioral interventions, and surgical options, the satisfaction rate following these methods varies. Approximately 49% of patients taking OTCs and 58% of patients under prescriptions experienced treatment failure [18].

Individuals with constipation reportedly have prolonged transit time, the upper limit of which is as high as 70h [2], which may be owed to dysfunction of the colonic smooth muscles. Interestingly, recent studies have shown an association between chronic constipation and dysbiosis, which is defined as an imbalance in the abundance of the natural gut microbiota. [2]. The gut microbiota balances the gut function, the alteration of which changes gut motility [7]. The composition of the intestinal microbiome in adults can get altered due to aging, stress, nutrition, treatment with antibiotics and other medicines, and genetic mutations. An altered presence of fecal microbe was found in constipated patients. A significant decrease in Provotella and an increase in Fermicutes was observed showing a varied diversity in the ecology of fecal microbe, in comparison to the conventional Lactobacillus or Bifidobacterium species [3]. Individuals with functional constipation also had remarkably elevated levels of Clostridium and Bifidobacterium species, among which C. sporogenes,

C. paraputrificum, C. fallax, and C. inoculum were in abundance among the Clostridium species [8]. A stable and well-balanced microbial composition of the gut is essential for good health, and any alteration in the biochemical activity of this microenvironment results in a deterioration of general health, with primary effects on the immune system [12].

Bowel incontinence and constipation are more common in individuals with diseases of the central nervous system. Neurological Bowel Dysfunction (NBD), where individuals lose their control over the bowel and endure severe constipation is more prevalent in people with neurodegenerative diseases than in the general population [10]. Interestingly, the association of intestinal diseases with neurodegenerative disorders such as Parkinson’s and Alzheimer’s is extensively studied and has found a significant correlation between PD and intestinal microbiota, owing to the increased presence of constipation in patients with Parkinson’s Disease (PD) [9]. Substantiating the relationship between gut dysbiosis and PD, constipation is regarded as the first Non-Motor Symptom (NMS) of the disease observed during the prodromal phase [11]. According to the Rome criterion, which is the internationally recognized criterion to define constipation, people with PD had 3 times more prevalence (59% v/s 21%) of constipation than people with any known neurological condition. Nearly 25% of the patients with Parkinson’s experience constipation before they develop the motor symptoms [9]. It should also be noted that these patients with PD, who falls under the Rome Criterion, have always not brought these to the attention of their healthcare providers. Also, the bowel-related quality of life in men and women with PD was respectively 60% and 46% worse in comparison with individuals without PD [16]. Although the criteria to define constipation varies depending on the clinical condition under observation, approximately 5-27% of the population in western societies suffer from constipation [13].

The World Health Organisation (WHO) defines probiotics as live yeast or bacteria that when administered at appropriate doses induce beneficial effects on health. According to WHO, probiotics are classified as milk-derived products inoculated with probiotic strain(s) with well-defined beneficial effects, non-milk products fermented with probiotic strain(s), non-fermented products with the addition of probiotic strain(s), and supplements containing probiotic strain(s) included in a galvanic preparation [15].

Although there are controversial opinions regarding the use of probiotics, there is growing evidence that probiotics are effective in treating constipation and enhancing bowel habits, which mainly relies upon the strain used in the probiotic product [14]. The application of probiotics in managing constipation has been studied primarily on the probiotics Bifidobacteria and Lactobacilli. Stool frequency and consistency have shown a significant improvement when investigated with B. lactis DN- 173010 when compared to a placebo in a population of constipated women [20]. Conversely, B. lactis with a different strain (NCC2818) showed no significant improvement either in bowel frequency or gut transit time in individuals with constipation. The efficacy of B. lactis DN-173010 has repeatedly been proven in various other studies. A combination of B. lactis DN-173010 and other yogurt strains such as S. thermophilus and L. bulgaricus in a fermented milk-containing product when administered on constipated women enhanced the stool frequency and relieved the abdominal pain or anal burning sensation associated with defecation [20]. In a pilot study conducted on 40 number of post-natal women, Lactobacillus casei strain Shirota (LcS) depicted alleviation in constipation and haemorrhoids formed following childbirth. Compared to the study arm, the placebo group showed no significant changes in constipation and haemorrhoids related symptoms and quality of life [21]. The same strain administered to a study group of 70 individuals with chronic constipation reported significant reductions in moderate and severe constipation, but there wasn’t any measurable difference in the degree of associated symptoms such as flatulence and bloating, both in the placebo and study group [22]. E. coli Nissle 1917 is another probiotic strain with proven efficacy in managing idiopathic chronic constipation [23]. Studies demonstrating the impact of the gut microbiome on the nervous system which forms the gut-brain axis indicate that modulation of the gut microbiota with probiotics alters intestinal motility and is hence a novel therapeutic approach in managing various gastroenteric disorders including constipation, in patients with neurodegenerative disorders. [19].

Although the mechanisms by which probiotic supplementations ease constipation and related symptoms are not vividly known, cumulative evidence from various clinical trials demonstrates the changes that probiotic administration produces on the gut microbiome [7]. The impact induced by metabolic by-products of the microbiota, which are physiologically active substances like Short-Chain Fatty Acids (SCFA) might contribute to variations in gut motility or gut function thereby alleviating constipation [24]. SCFA produced such as butyric acid, propionic acid, and lactic acid lowers the pH in the colon, thereby enhancing the peristalsis and decreasing the intestinal transit time [23]. Additionally, supplementation of certain probiotic strains increases the concentration of the endogenous gut microbiome. For instance, the concentration of Bifidobacteria in the gut was expanded by the incorporation of Bifidobacterium lactis GCL2505 or Lactobacillus casei Shirota. These shreds of evidence are suggestive of the influence of probiotics on the gut microbiome, but the underlying pathological process isn’t clearly defined yet [25]. With a variety of probiotic products available in the market for public consumption, adequate care should be taken when probiotics are consumed daily.

With varieties of probiotics booming in the market and handily available to the public for consumption and the unreliability that exists regarding its use, this review focuses on the influence of probiotics in enhancing the bowel habits of individuals with constipation in the adult population. There is only a much smaller number of articles available in scientific data platforms relevant to the title of the review published in the last 10 years, specifically based on the keywords used in the search strategy. This review focuses on RCTs from the last 5 years, that is published online.

4. Methods:

4.1. Ethical Approval:

This research doesn’t require a full Ethical Committee Review.

4.2. Search Strategy:

This systematic review followed the PRISMA 2020 flow diagram as the search strategy to sort relevant studies for the review. Scientific platforms with electronic databases such as PUBMED Advanced Search, Cochrane Library-Cochrane Reviews and Registries (https://www.clinicaltrialsregister.eu/, https://clinicaltrials.gov/) were searched for the journals containing the keywords. The search was restricted to papers in the

PRISMA 2020 Flow Diagram for New Systematic Review.

From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71

To avoid the production of biased results, Meta-analysis was not carried out due to the divergence in the types of intervention used in the studies. Although the study intended to perform a subgroup analysis of the potential factors that could influence the clinical outcomes of the RCTs such as the type of strain, age of the study population, and underlying clinical conditions, it wasn’t possible with the current view due to the limitation in the data available. The review performed an analysis of Bias based on the Revised Cochrane Risk of Bias Tool for Randomized Trials (ROB2) and 7 out of the 9 studies included in the review depicts various forms of Bias[47][48].The results are summarised as follows:

4.3. Search Outcomes:

The search identified 368 studies from PUBMED and Cochrane Library. From registries, the search identified 10 studies. The search did not identify more than one systematic review published online in the last 5 years specifically for probiotics for constipation in adults. All the other reviews found on the databases had several other inclusion strategies. The studies were screened to meet the inclusion criteria and 9 RCTs that met the requirements were selected for this review. This review generally included studies that had the age of the population from 18-75 years (Early, Mid, or Late Adulthood) and experienced Functional Constipation under Rome III or IV criteria and used only either probiotics or placebo as intervention. All the included studies don’t define any other characteristics for their study population. All the RCTs included in this research are peer-reviewed publications.

5. Results:

5.1. Study Description:

All the studies included in this review are double blinded-RCTs. The sample size ranged from 45 -171 with a total of 852 participants in all the studies. The studies were performed on adult populations aged 18-75 years. The studies were conducted for durations of a minimum of one week to a maximum of 8.6 weeks. 4 out of the 9 studies used a combination of bacterial strains whereas the remaining used single strains. Among the 5 studies, 2 of them used two different species of Bifidobacterium (B.animalis and B.lactis), and 2 used two different strains of Bacillus coagulans (B. coagulans Unique IS2 and B. coagulans SNZ 1969) and one study used Lactobacillus reuteri DSM 17938 as intervention.

Study Products: The studies used chocolates, capsules, sachets of granulated formulation, or fermented milk infused with or without probiotic culture as supplements for probiotic or placebo.

All the studies assessed the alleviation of constipation and related symptoms. 8 out of 9 studies reported treatment success in terms of stool consistency and more frequent bowel movements. One study reported treatment failure with probiotics.

Table 1. Characteristics of the studies included in this review.

5.2. Study Outcomes:

This systematic review analyses the efficacy of probiotics in enhancing the bowel habits of individuals with constipation by assessing the study outcomes of the selected RCTs, which are as follows:

Stool Consistency: 2 studies [25], [26] measured stool consistency according to the Bristol Stool Scale Form. The stool consistency, which was measured at weeks 4 and 8 [24] and weeks 3 and 4 [25], showed a significant improvement in the probiotic group compared to the placebo. The group treated with B. coagulans Unique IS2 reported a mean stool score of

2.28 ± 0.60 at week 3 and 3.02 ± 0.57 at week 4. The mean stool score for the placebo group was 2.06 ± 0.43 and 2.65 ± 0.58 at weeks 3 and 4 respectively. The results showed a P value of 0.041 for week 3 and 0.021 at week 4 owing to the significant increase in the number of participants with normal stool in the probiotic group (98% v/s 74%).

For the group treated with combination strains of Streptococcus thermophilus MG510 and Lactobacillus plantarum LRCC5193, a mean stool score of 3.7 ± 1.1 vs. 3.1 ± 1.1 at 8 weeks, with P=0.002 was reported.

Stool Frequency: 3 studies [27], [30], and [33] assessed the stool frequency of the study population based on the number of spontaneous stools per week. A bowel frequency of

0.90 ± 0.73 (week 1), 1.66 ± 1.81 (week 2), 4.16 ± 1.98 (week 3), and 5.98 ± 1.57 (week

4) spontaneous stools per week was reported for the group receiving B. coagulans Unique IS2 capsules. Also, a significant increase in the mean frequency of spontaneous stools per week was observed [27].

The probiotic group which received Lactobacillus reuteri DSM 17938 (LR DSM 1793 reported an increase in stool frequency in addition to enhanced defecation and a reduction in the amount of time spent in the toilet. According to the Constipation Scoring System (CSS), the P value for stool frequency was 0.0353, for Incomplete defecation was 0.0124 and the time spent in the toilet had a P<00001. 

For the study group that received Hexbio^®, the median stool frequency increased to 6 times/ week compared to baseline defecation frequency, which was 3 times/week at the start of the study for both the placebo and probiotic group.

One RCT [27] assessed the severity of constipation-related symptoms such as defecation pain and abdominal pain as secondary outcomes. The mean CSS score for painful evacuation effort for patients treated with B. coagulans Unique IS2 at visit 3 was 1.16 ± 0.58 and that of placebo was 1.50 ± 0.84 (P=0.021), whereas the score dropped to 0.66 ± 0.52 and 0.98 ± 0.62 at visit 4 for probiotic cohort and placebo respectively. (P=0.006).

At visit 3, the mean CSS score for abdominal pain for the probiotic group was 0.94 ± 0.68, and that of the placebo was 1.1 ± 0.84. (P=0.038). At visit 4, the score dropped to 0.38 ± 0.49 for the probiotic cohort compared to that of the placebo which was 0.8 ± 0.81 (P=0.002).

Treatment with a different strain of Bacillus coagulans (SNZ 1969) decreased the Colon Transit Time (CTT) by 13.6 hours during the experimental period whereas the CTT increasedby 6.1 hours in the placebo group (P=0.031). In this study both placebo and probiotic groups showed improvement in the weekly mean CSBM score. But the CSBM score was more than double in the probiotic group at weeks 2 (P= 0.045) and 9 (p = 0.038) [28].

One RCT [29] analysed the efficacy of a multi-strain probiotic blend on constipation-related gastrointestinal symptoms based on PAC-SYM and PAC-QoL questionnaires. The study reported a decrease in the mean area under the curve for the probiotic group for constipation-related symptoms such as bloating, abdominal discomfort, flatulence, and burbling on post-hoc analysis.

One RCT [31] reported treatment failure with probiotics. The study that used Bifidobacterium lactisNCC2818 as the intervention observed no significant changes in gut transit time and gut microbiota composition in the fecal sample of the participants. The gut transit time for both probiotic and placebo groups showed no significant change from baseline to 2 weeks (−11.7 hours, SD 33.0 hours vs−12.9 hours, SD 33.6 hours P= 0.863) or at 4 weeks (−20.4 hours, SD 32.5 h vs−8.7 hours, SD 33.8 hours, P= 0.103).

One RCT [32] assessed the effect of a multiple-strain probiotic in alleviating the feeling of incomplete defecation by analysing its effects on redox and inflammatory responses in individuals with intestinal constipation. The study reported partial alleviation of the feeling of incomplete defecation (P=0.012) in more than 25% of bowel movements in the probiotic group compared to the placebo.

Constipation-related symptoms such as straining during defecation, lumpy hard stools, and the feeling of incomplete evacuation showed significant ease on treatment with the multi- strain microbial preparation called Hexbio^® and the single strain B.animalis in comparison to the placebo [33] [34]. The P values for the former three symptoms were ≤0.001. Although not statistically significant, a higher proportion of the participants in the multi-strain probiotic group experienced an improvement in anorectal blockage sensation (66.7% vs 39.1%) and decreased effort to defecate by manual maneuvers (66.7% vs 39.1%) compared to the placebo [33]. A statistically significant improvement in anorectal blockage was observed in the treatment group which received B. animalis (P=0.014) [34].

Adverse Events: None of the studies reported any grades of adverse events during the course of the trial or even after

6. Discussion:

6.1  Principal Findings:

This systemic review was aimed at finding out whether the use of probiotics could be of any help to the adult population experiencing constipation. The primary findings from the RCTs included in this review suggest that the use of probiotics could ameliorate constipation and related symptoms. The clinical relevance of the use of probiotics remains controversial due to the limited data available.

Collectively, the findings from the studies suggest that 1) Probiotics enhance stool frequency and consistency 2) Alleviate abdominal discomfort and pain 3) Improve intestinal motility 4) Relieve anorectal obstruction, straining during defecation, and aid in ameliorating bowel evacuation, but all the outcomes are exceptionally strain specific. Based on these findings, the proposed mechanisms by which probiotics benefit individuals with constipation may include 1) alteration of the intestinal microbiota of individuals with constipation 2) alteration of gut sensation and motility function 3) regulating the intraluminal environment such as lowering the intestinal pH [38].

6.2. Analysis of the findings:

Although the study [25] reported positive results for the probiotic group, complete spontaneous bowel movements did not show much variation in both cohorts, which shows that the strain is less specific for the complete evacuation of the bowel contents [36]. But L.plantarum was proven to be efficacious in inducing complete bowel evacuation when administered with Bifidobacterium breve, or Bifidobacterium lactis [37]. Novel studies conducted on mice using another strain of L.plantarum called Lp3a effectively relieved constipation and related symptoms by supposedly altering bile acid synthesis and amending methane metabolism. The ANOSIM method done on the pre and post treatment fecal samples by 16S rRNA sequencing revealed that L.plantaurm doesn’t directly affect the microbial diversity in constipated mice [38].

Apart from Streptococcus and Lactobacilli, Bifidobacterium is the most extensively researched probiotic for constipation. However, the findings are suggestive that the efficacy of the probiotic is strain specific. For instance, B.animalis was effective in relieving constipation related symptoms whereas B. lactisNCC2818 was found to be totally ineffective for the same cause[31], [34]. B. animalis spp. lactis DN-173 010 accelerates gut transit time and relieves constipation. The strain specificity of probiotics is explicitly exhibited by various other strains such as B. lactis BB-12^® and B. lactis HN019 where the latter one showed moderate to large effects in relieving constipation. The former enhanced the average defecation rate but did not accelerate the defecation frequency in individuals with normal bowel movements [40]. B. lactis BB-12^® is postulated to modulate the composition of the microbiome by inhibiting the pathogens and increasing the number of Bifidobacterium, thereby potentially modifying the intestinal microenvironment [41].

According to the search results from scientific data platforms, the novel spore-forming B.coagulans has been investigated for treating constipation for less than a decade. The study results to date suggest that B. coagulans is effective in alleviating constipation in adults but with no underlying conditions. The B.coagulans Unique IS2 specific strain exhibits huge statistical significance in enhancing stool frequency and consistency and alleviating related symptoms such as incomplete defecation and abdominal pain in adults with constipation[28]. When administered as a supplementary therapy with Lactulose, the time required to relieve constipation was reduced than when lactulose was given as monotherapy. In various other strains such as B. coagulans GBI-30 6086 and B. coagulans 90, the two strains of B.coagulans spores failed to alleviate loperamide induced constipation in mice [35]. However, animal models of Bacillus coagulans BC01 (BC01) depict that the adverse effects of constipation, specifically induced by loperamide are effectively reversible. Another strain, B. coagulans LBSC is competent enough to create a normal intestinal microenvironment. This is achieved by up regulation of Actinobacteria and Firmicutes and down regulation of Bacteroides, Proteobacteria, Streptophyta, and Verrucomicrobia which would modify the metabolic pathways, thereby enhancing the colonic transit time [42].

The percentage of responders with reduced CTT was significantly higher in the adult population when treated with B. coagulans SNZ 1969. Interestingly, this strain of B.coagulans did not significantly alter the fecal pH even though it altered the composition of the gut microbiota[28].

Symptoms related to gas production and dysbiosis such as abdominal pain, bloating and incomplete defecation eased when treated with LR DSM 17938 in patients with Functional Constipation but without any abnormal colonic patterns. Use of this strain, particularly in constipated women has reduced the use of enema or laxatives [30]. On average, the study reported a 40% reduction in the use of laxatives among the study population. Considering the duration of the trial, this definitely is a promising result. But, if the study duration a definite period to obtain therapeutic efficacy is still questionable.

The administration of the same strain on a 4 week trial has depicted stool inconsistency after the withdrawal of the intervention [44]. Also, in the present study, LR DSM 17938 has shown a significant difference only after the 60^th day from the day of probiotic administration. Thus, in order to obtain optimal efficacy, the duration of treatment is an inevitable variable to be considered. However, based on the CSS, PAC-QoL, and Constipaq score, the study points out the fact that clinical investigations should not only be focused on the classical symptoms, rather the non-classical symptoms such as abdominal pain, discomfort, and bloating need to be addressed [30]. The preferential retention of gas within the small bowel, as well as the effects of methane on gut motility, visceral sensation, and regularity, might also be conceived as abdominal bloating, which then might induce pain and discomfort [43].

A multi-strain probiotic study that selectively blended strains with previously proven efficacy such as Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium animalis subsp. lactis strains Bl-04, Bi-07 and HN019 reported less digestive discomfort for the probiotic group compared with the placebo. In this study, the placebo exhibited the placebo effect by functioning similarly to the probiotic group. However, the post hoc analysis revealed that the statistical results favoured the probiotic cohort[29]. It should be noted that no two probiotic strains can have similar efficacy. Animal models including Lactobacillus strains demonstrate that higher GI transit rates can be achieved even with Loperamide-induced constipation irrespective of the dose of the probiotic administered [45]. Multi strain animal models with Lactobacillus and Bifidobacterium suggest that the intestinal concentration of MTL and VIP can be restored as well as that of VIP, SS, and ET-1 can be reduced, which in turn regulates the secretory hormones of the intestinal tract and thereby relieves constipation. But it should be noted that the secretion of the gastrointestinal regulatory hormones varied in a dose dependent manner [45]. 

Multispecies probiotics are proposed to be effective in modulating the gut microbiota of constipated individuals who have a significantly lower abundance of Bifidobacterium and Lactobacillus and more pathogenic bacteria and fungi [45]. This study [32], unveiled that individuals with functional constipation may benefit from the enzymatic antioxidant activity of the probiotics. Although both the probiotic and control groups exhibited a reduction in GPX and GST activities, the rate of reduction in the probiotic group was much lower compared to the placebo (25% v/s 31%). Also, an examination of the fecal samples revealed a relative abundance of Firmicutes in the probiotic cohort. Although this multi strain blend may appear to be beneficial, it should be noted that no significant changes were observed between both groups in terms of Rome IV criteria, Stool consistency, or evacuation frequency. However, the probiotic cohort has shown a reduction in the prevalence of individuals with incomplete defecation and blockage sensation [32]. Interestingly, this study also points out that factors such as physical activity, alcohol intake, changes in diet, and water intake are contributing elements that would modify the microbiota involved in persuading constipation and related symptoms [5][32]. 

The microbial cell preparation containing Lactobacillus and Bifidobacterium was proven efficacious in improving stool consistency and frequency in constipated individuals. But the differences were not statistically significant [33].

6.3. Gaps in Current Knowledge:

Probiotics as monotherapy or in combination seem promising in managing constipation and related symptoms but with the existing evidence, a carefree application of probiotics isn’t relatively easy due to the gaps in current clinical knowledge:

1. The underlying exact mechanisms by which probiotics ameliorate constipation are still not evident to establish a strong link between probiotic strains and constipation. Also, the heterogenicity of the studies done to date makes it incomprehensive to establish an algorithm or guideline for constipation based on probiotic therapy. 

   
   

2. The composition of intestinal microbiota in constipated individuals and changes following probiotic therapy has so far been assessed by fecal samples. Although it’s a standard procedure, it should also be noted that the association of colonic mucosa with intestinal bacteria is prognostic for constipation. Hence microbiota analysis based on colonic biopsy might reveal more precise information for definitive taxa related to constipation. 

3. The early development of constipation in various medical conditions especially in neurodegenerative disorders like Parkinson’s Disease can further be postulated as a diagnostic approach in identifying the early stages of the disease.

4. Studies exclusively defining probiotics and constipation in adults are very limited. Current results are invigorating but there’s a need for large population based RCTs.

7. Conclusion:

Probiotics, which are defined as non-pathogenic microbes, can have beneficial effects on the host health when administered at adequate amounts. The consumer market provides probiotics in various names to the public such as Yakult (L. casei Shirota), Actimel (L. casei DN 114 001), Activia (B. lactis DN- 173010) to name a few. These are used by the general population a protective aid for their gastrointestinal system. Numerous studies have reported the ineffectiveness of probiotics in treating constipation in children. So, it’s high time that the general population is made aware of the safety profile of these products. Although an externally visible change may not be seen, it should be emphasized that the consumption of probiotics from a very young age may or may not induce beneficial changes in the gut.

The current data available for using probiotics to manage constipation in adults is inconclusive. However, the studies do conclude that the efficacy of the probiotic depends on the specific strain that is used. Additionally, the consumption of probiotics has definitely improved the quality of life in adults with constipation. The current view requires more of large population-centered and strain-specific studies to draw a definite picture of the safety profile for the use of probiotics. Also, studies related to the beneficial effects of each strain for different categories of the population can bring cumulative data for the immunotherapeutic application. The efficacy of combination strains is not profound in the current view.

Although the safety profile for the use of probiotics remains good with no adverse effects reported, the current data available is not sufficient to recommend the use of probiotics for people who are at risk. Hence, with the current view, the application of probiotics on populations at risk might be harmful, especially in immunocompromised individuals.

With media advertising information regarding gut health and the use of complementary and alternative medicines such as probiotics, the pros and cons of the consumption of such products on a day-to-day basis should be made aware to the public. Based on the current scientific shreds of evidence, the therapeutic recommendation of probiotics for treating constipation remains investigational. The clinical uncertainty pertaining about its use points towards conducting large scale RCTs and the possibility to clarify the influence of such interventions in bringing out a definite outcome. This review recommends conducting more strain-specific studies at different levels of the population.

This review is performed independently by the researcher based on the published papers, hence publication bias can’t be avoided.

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9. APPENDIX A

DECLARATION

 This work is original and has not been previously submitted.