Study referenc

e

Study characteristics

Patient characteristics

Intervention (I)

Comparison/ control (C)

Follow-up

Comments

Gupta, 2021

RCT, secondary care, India.

This study was solely funded by Advanced Enzyme Technologies Limited, Thane (India).

The authors have no conflicts of interest to disclose.

Inclusion criteria: (1) Male and females (18–65 years) with diagnosis of IBS as per Rome IV criteria associated with following symptoms for

more than last 3 months; like abdominal discomfort such as

mild pain, cramping, bloating, altered bowel habit indicated

by frequent diarrhoea or constipation and functional dyspepsia;

(2) written informed consent by study participants.

Exclusion criteria: Subjects those were on antibiotics or

laxatives within the preceding 6 weeks, Symptoms of IBD, acute

GI tract infection, fever, abdominal mass, signs of bowel

obstruction, history of colon cancer or diverticulitis, infection

from human immunodeficiency virus (HIV), hepatitis B virus

(HBV), and hepatitis C virus (HCV), celiac disease, scleroderma

and gastroparesis and hypothyroidism were excluded from the

study (Supplement: Details of Exclusion and Withdrawal

Criteria, 

http://links.lww.com/MD/F368). In addition, subjects

having adverse effects or serious adverse effects, pregnancies, disease emergencies, concomitant therapy, and study protocol violation are considered for

withdrawal of subjects from the trial.

Intervention: 20 patients Control group: 20 patients

Groups comparable at baseline for gender: I male 65%, C male 75% Age: I 36 y, C 35 years

Also for height, weight, BMI.

The investigational product (IP) was the active ingredient, B coagulans LBSC mixed with the excipient. The strength of the active ingredient was 2 billion spores per gram per sachet, which was supplied by Advanced Enzyme Technologies Ltd., Thane, India.

The placebo contained only excipient, maltodextrin (1.00 g).

Treatment duration was up to 80 days and total study duration did not exceed 90 days.

With total 2 patients lost to follow up (dropped out) 1 in each group; trial was completed with total 38 PP population.

Reasons not described.

Outcomes: Digestive Symptom Frequency Questionnaire (DSFQ) on 5-point Likert scale (0=never, 1 1

episode/wk; 2

3 episodes/wk; 3≥

3 episodes/wk; 4=daily episodes), change in gastrointestinal symptom’s severity using IBS severity scoring system (IBS-SSS) and change in stool consistency using Bristol

stool form scale. Plus adverse events and The QoL was assessed based on yes or no responses for pain scale on abdominal pain, diarrhoea, constipation, bloating and

flatulence, 

vomiting and nausea, perception of

mental well-being, and influence on daily life.

Skrzydlo, 2020

RCT, outpatients clinics, Poland. Funding: This research was funded by the grant financed by Biocare, Copenhagen, Denmark (the principal investigator—B. Cukrowska).

Conflicts of Interest:

B.C. has served as a speaker for Nutricia, Danone, Bayer, Apotex, Polpharma, and Mead

Johnson. J.G. is the co-founder of Biocare Copenhagen,

a company acquired by DSM Nutritional Products in 2017, but was not involved in conducting the study and data analyses. Other authors declare no conflict of interest.

dysfunctions,

serious neurological disorders, psychosis, respiratory disorders such as asthma, chronic obstructive pulmonary disease, hyper- or hypothyroidism); chronic bowel disorders other than IBS, including inflammatory bowel diseases, gastroenteritis, stomach and duodenal ulcers, celiac diseases; pregnancy

or lactation; diagnosed lactose intolerance; the use of motility drugs or dietary fiber supplements

within 2 weeks before study start; plan to have surgery during the time of the study; a history of

alcohol or drug abuse, taking anti- coagulant medications, participation in another clinical trial within

last three months.

Intervention: 40

Control group: 40

There were no statistically significant differences between the synbiotic and the placebo groups in gender, age, physical development and IBS severity.

Gender: I 71% female, C 73% female Age: I 43 years, C 37 years.

IBS severe: I 60%, C 70%

IBS SSS: I 318, C 326

The synbiotic preparation in the form of sachets contained multi-strain probiotic mixture of three Bifidobacterium and two Lactobacillus species (Table 1). The total number of colony-forming units (CFU) per sachet was five billion. The composition of probiotic bacteria resulted from an earlier preliminary study in which positive effects in IBD patients were observed [26]. Patients obtained a mixture of four strains (Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium

bifidum and Lactobacillus acidophilus) 

that were used in the present study. Additionally, the probiotic mixture was enriched with Lactobacillus rhamnosus FloraActive 19,070 strain, which when administered to babies with infant colic significantly reduced the time of crying and anxiety compared to the control group [27]. We decided on a dose

of 10 billion/day, taking into account the results of the meta-analysis assessing the optimal dose of

probiotics in IBS, which showed that the dosage of 109–1010 CFU/day may be a reference range [28].

The synbiotic preparation also contained prebiotic scFOS from Actilight® (Beghin Meiji, Marckolsheim, France) in a dose of 947 mg in each sachet. scFOS was obtained from sugar beet by a

bio-enzymatic reaction and contained 44% of glucose linked 2 units of fructose (GF2), 46% GF3, and

10% GF4. The molecular weight of scFOS was 603 g/mol, and purity of scFOS was at least 95% of

dry substance.

The placebo sachets contained 978 mg of maltodextrin comparable in color, texture

and taste to the synbiotic mixture.

Length of follow up: 8 weeks.

After the 4-week treatment (visit II), three patients from the synbiotic group and five patients from

the placebo group were excluded because of antibiotic treatment (n = 1 in the synbiotic groups and

n = 2 in the placebo group), no telephone contact (n

= 2 in the synbiotic

group and n = 2 in the placebo group) and one urgent hospitalization due to heart failure in the placebo group. In the next 4 weeks, two patients from each group were excluded from the study. Finally, a total of 68 patients (35 receiving the synbiotic preparation and 33 placebo) finished the study.

IBS-SSS, IBS-GIS,

IBS-AR , Bristol stool scale (1-7), severity of pain, flatulence stool pressure (5 points likert scale).

Shi, 2020

Type of study: RCT

Setting and country: hospital / outpatient department, China

Funding and conflicts of interest: This study was funded in full by the Wu Yingkai Foundation for Medical Research and Development, Beijing (grant numbers XD201907). The authors declare no competing interest.

Inclusion criteria:: (1)25-70 years of age; (2) repeated episodes of abdominal pain, abdominal distension, or bowel habit abnormalities (constipation, diarrhea, or mixed constipation and diarrhea), with

a period of more than 6 months; (3) no past history of any chronic disease; and (4) no history of abdominal surgery.

Exclusion criteria: (1) contraindications for colonoscopy, disable to tolerate colonoscopy and bowel preparation; (2) taking drugs affecting the

gut microbiota within a month before the selection (e.g.,

antibiotics, antiacid drugs, and probiotics) and drinking

alcohol; (3) colonoscopy results of colon malignant or benign

tumor, colorectal enteritis, colorectal ulcers, and inflammatory bowel disease; and (4) pregnant women.

N total at baseline: Intervention: 25

Control: 25

Important prognostic factors2:

Age ± SD: I: 41 +/- 11

C: 43 +/- 12

Sex:

I: 64% F

C: 76% F

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test): Medilac-S (live combined Bacillus subtilis and Enterococcus

faecium enteric-coated capsules, 500 mg per time, three times

per day, Hanmi Pharm Co. Ltd., Beijing, China) for 4 weeks.

Describe control (treatment/procedur e/test): unknown.

Length of follow-up: 4 weeks.

Loss-to-follow-up: ?? Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Gastrointestinal symptom rating scale

(GSR’S) covers 15 gastrointestinal symptoms, each classified

into four severity categories (score of 0–3).

Sadrin, 2020

Type of study: RCT

Setting and country: office-based physicians and a hospital, France

Funding and conflicts of interest: This study was fundedby OSEO Innovation- Bpifrance (MaisonsAlfort, France) and Laboratoire Denel- Codifra (Le Chesnay, France). Stéphane Sadrin is an employee of Laboratoire Denel- Codifra (Le

Chesnay, France), which supplied probiotics and the placebo for the research. The remaining authors disclose no competing interests.

Inclusion criteria: aged between 30 and 60 years old; diagnosed for IBS according to Rome III criteria; presented with a negative coprological and inflammatory balance (negative CRP blood test) for over 6 months

Exclusion criteria: l if they presented with an organic intestinal disease, a severe or

active disease with multiple treatments, intestinal parasitic infection in the last 6 months, inflammatory bowel disease or a history

of previous abdominal surgery (except appendectomy, caesarean birth, tubal ligation, hernia). In addition, subjects were excluded

if they changed their medication in the last 2 months, took probiotics in the last 2 months or antibiotic therapy in the last 30

days, received current antidepressant or antipsychotic treatment,

and received antimycotic and antiseptic treatment or treatment affecting gastrointestinal transit as well as chronic use of antalgic

and antispasmodic medications.

Additional exclusion criteria are

detailed in the LAPIBSS protocol.

N total at baseline: Intervention: 40

Control: 40

Important prognostic factors2:

Age ± SD:

I: 49 +/- 8

C: 49 +/- 8

Sex:

I: 73% F

C: 70% F

Groups comparable at baseline? Yes for age, weight, sex ratio, abdominal pain, bloating, flatus, rumbling, composite score, stool frequency, stool consistency.

Describe intervention (treatment/procedure/test):

8 weeks

The study product

was provided in the form of vegetable capsule containing a blend

of two viable lyophilized L. acidophilus strains: L. acidophilus NCFM

(FDA GRAS Notice 000357,

strain number ATCC SD5221, Danisco

Inc. Madison, Wisconsin, United States) and L. acidophilus subsp. helveticus LAFTI L10 (strain number CBS 116.411, Lallemand Health Solutions, Blagnac, France). This mixture of two probiotic strains

provides for each 2.5 × 109 colony-forming unit (cfu) for a total

of 5 × 109 cfu per capsule. Formulations of the indistinguishable

investigational products are detailed in the 

supplementary material (Table S-1). These products were specially manufactured for

the study by Laboratoire Denel-Codifra (Le Chesnay,

France). The trial dose was 2

capsules/day taken orally; one in the morning and

the other one in the evening with a full glass of water half an hour

before eating

Describe control (treatment/procedur e/test):

8 weeks

Placebo. Unknown.

Length of follow-up: 9 weeks

Loss-to-follow-up: Intervention:

N 1 (2,5%)

Reasons (describe) unknown.

Control:

N 0 (0%)

Reasons (describe)

The

primary outcome was abdominal pain score assessed with a 100-mm visual analogue scale. Secondary outcomes included scores of bloating, flatus and rumbling assessed with a 100-mm visual analogue scale,

a composite score and bowel habits.

Martoni, 2020

Type of study: RCT

Setting and country: outpatients, India

Funding and conflicts of interest: his research was funded by UAS Laboratories LLC.

Christopher J. Martoni and Gregory Leyer are employees

of UAS Laboratories but were not involved in the study conduct, data management or statistical analysis.

Inclusion criteria: Healthy adults, aged 18 to 70 years, meeting Rome IV diagnostic criteria for IBS were recruited

Exclusion criteria: Participants with organic disease, a history of surgical resection of the stomach, small or large intestine,

a history of inflammatory bowel disease, complications from infectious enteritis, hyperthyroidism or

hypothyroidism, a history of diet-

based intolerance, drug or alcohol 

abuse within the past 6 months,

a history of malignant tumors, severe depression or anxiety disorder, or uncontrolled hypertension

were excluded. Additional exclusion criteria included individuals with unstable medical conditions,

type I or II diabetes, a history of cancer or abdominal surgery, immunocompromised conditions, or an active eating disorder. Smokers, defined as ≥ 1 cigarette a day and individuals consuming > 2

standard alcoholic drinks daily over the prior 3 months were excluded

N total at baseline: Intervention: 110 en 111

Control: 112

Important prognostic factors2:

Age ± SD:

I: 39 (12) en 42 (11)

C: 38 (10)

Sex:

I: 52% en 47% F C: 50 % F

Groups also comparable at baseline for BMI, BP, GAD, PHQ, alcohol consumption.

Describe intervention (treatment/procedure/test):

The probiotic study products consisted of either

L. acidophilus DDS®-1 or B. animalis subsp. lactis UABla-12™. L.

acidophilus DDS-1 or B. lactis UABla-12 capsules, which each contained a potency of not less than (NLT) 1 × 1010 CFU/capsule, were formulated with

lyophilized probiotic and microcrystalline cellulose.

Describe control (treatment/procedur e/test):

Placebo capsules were formulated with microcrystalline cellulose.

Length of follow-up: 42 days intervention

Loss-to-follow-up: Intervention:

N 4 + 4 (%)

Reasons (describe) unknown

Control:

N 3 (%)

Reasons (describe) unknown

Abdominal pain severity (APS NRS), IBS symptom severity (IBS SSS), stool form and frequency (Bristol Stool Scale), IBS related quality of life (IBS QoL) and perceived stress (PSS).

Lewis, 2020

Type of study: RCT

Setting and country: open population, 

Canada

Funding and conflicts of interest: This research was funded by Lallemand Health Solutions (LHS).

LHS owns Bifidobacterium longum R0175 and Lactobacillus paracasei HA-196. TAT, RB and

AP are employees of Lallemand Health Solutions. LHS was involved in the design of the study, revising the manuscript and decision to publish the results but was not involved in data collection and analyses, or writing the

manuscript. The corresponding author oversaw collection and analysis of data and had final responsibility for the decision to submit

for publication.

Inclusion criteria:: aged 18 years or older, IBS diagnosed according to the Rome III criteria, and willingness to

discontinue probiotic 

consumption for the duration of the study

Exclusion criteria: Participants were excluded if they used medications to manage IBS symptoms or narcotics in the past month, history of gastrointestinal surgery, gastrointestinal disease (except hemorrhoids and uncomplicated diverticula) or family history of colorectal cancer, inflammatory bowel disease, or

celiac sprue.

N total at baseline: Intervention: 84 + 86

Control: 81

Important prognostic factors2:

Age ± SD:

I: 42 (12) and 42 (17)

C: 42 (16)

Sex:

I: 80 and 74% F

C: 79% F

Groups are comparable at baseline for type of IBS, race, ethnicity, gender and age.

Describe intervention (treatment/procedure/test):

Each probiotic capsule contained 10 × 109

colony forming units (CFU) of either freeze-dried

B. longum (Lot Numbers: NH131210-1VB and NH151104-ICP) or L.

paracasei (Lot Numbers: NH131217-1VB and

NH151106-ICP), with potato starch and magnesium stearate as excipients.

Describe control (treatment/procedur e/test):

The placebo (Lot Numbers: NH131226-ISC and NH151028-ICP)

contained only potato starch and magnesium stearate.

Length of follow-up: 8 weeks

Loss-to-follow-up:

Intervention:

N 4 + 3 / 3 + 1 (%)

Reasons (describe) Withdrew or withdrawn consent

Control:

N 5 / 2 (%)

Reasons (describe) withdrew or withdrawn consent

IBS symptom severity (IBS-SSS), general health (SF 36), psychological well – being. HADS.

Kim, 2020

Type of study: RCT

Setting and country: secondary care, Korea

Funding and conflicts of interest: This research was supported by research fund

from the Clinical Research Institute of the Seoul National University

Hospital. This work was also carried out with the support of ‘‘Cooperative Research Program for Agriculture Science & Technology Development (Project No.

PJ01123002)’’, Rural

Development Administration, Republic of Korea. The authors have no financial conflicts of interest

to declare.

Inclusion criteria: (a) age between 18 and 75 years, (b) diagnosed with 

diarrhea-dominant IBS according to Rome II criteria

(c) without any organic abnormalities by physical and laboratory examination during the screening period.

Exclusion criteria:: (a) intolerance to probiotics or lactose, (b) pregnancy or lactation, (c) severe systemic illness (liver cirrhosis, congestive heart failure, chronic renal failure, angina, uncontrolled hypertension, endocrine disorder, metabolic disorder, or malignant tumors), (d) history of

inflammatory bowel disease or psychiatric disorder, (e) alcohol or drug addiction, (f) previous abdominal surgery other than appendectomy, (g) being judged ineligible for articipation in clinical trials by clinicians

N total at baseline: Intervention: 32

Control: 31

Important prognostic factors2: in supplement

Age ± SD:

I:

C:

Sex:

I: % M

C: % M

Describe intervention (treatment/procedure/test):

Combined probiotics, which included 5 strains of probiotics (Bifidobacterium longum BORI,

Bifidobacterium bifidum BGN4, Bifidobacterium lactis AD011, Bifidobacterium infantis IBS007, and

Lactobacillus acidophilus AD031) were used in this study. A capsule was composed of a total of 5 9 109 viable cells in a lyophilized powder form with the

other ingredients including maltodextrin, corn starch, and

silicon dioxide. 3x daily

Describe control (treatment/procedur

e/test):

The placebo capsule had almost the same contents as the active medication, even though the bacteria

were replaced with maltodextrin.

3x daily Groups comparable at baseline? There were no significant differences in the baseline clinical and laboratory characteristics between the probiotic a placebo groups

Length of follow-up: 8 weeks 

Loss-to-follow-up: Intervention:

N 0 (%)

Reasons (describe)

Control:

N 0 (%)

Reasons (describe)

IBS symptoms, stool frequency.

IBS sss IBS qol abdominal pain

Gayathri, 2020

Type of study: RCT

Setting and country: secondary care, India.

Funding and conflicts of interest: not reported

Inclusion criteria: Subjects

of both sex, aged above 18 years, and meeting ROME III

criteria of IBS were included in the study.

Exclusion criteria: Subjects with organic intestinal diseases; pregnant women and children; immunocompromised individuals; food allergies; with comorbid conditions like diabetes, hypertension, and cardiovascular diseases; and subjects on prior probiotics therapy were excluded

N total at baseline: Intervention: 52

Control: 48

Important prognostic factors2:

Age ± SD:

I: 42(15)

C: 40 (13)

Sex:

I: 39% F

C: 29% F

IBS-D 65%

Groups comparable at baseline? All the baseline characteristics of the subjects are similar in

both the control group and the treatment group and showed no significant differences

Describe intervention (treatment/procedure/test):

Standard treatment for 2 weeks along with

Saccharomyces cerevisiae CNCM I3856 (2 × 109 c.f.u)

capsules twice daily for 8 weeks.

Standard treatment for IBS included antidiarrheal— loperamide 2 mg BD 2 weeks for diarrhea predominant IBS, antispasmodic—dicyclomine 20 mg QID for 2 weeks for constipation predominant IBS and for IBS-M subjects, treatment

depends on the patient’s presentation (antidiarrheal/laxative)

Describe control (treatment/procedur e/test):

standard treatment for IBS for 2 weeks along with placebo twice daily for 8 weeks.

Length of follow-up: 10 weeks

Loss-to-follow-up: Intervention:

N 4 (%)

Reasons (describe)

Control:

N 4 (%)

Reasons (describe)

IBS symptoms (abdominal pain likert scale 1-7) and adverse events.

Barraza, 2020

Type of study: pilot RCT

Setting and country: secondary care, Mexico

Funding and conflicts of interest: This study received no funding.

The authors declare that they have no conflicts of interest.

Inclusion criteria: age range 18–59 years, meeting Rome IV criteria for the IBS-D-predominant or mixed subtype [24], accepting participation in the study, and signing of informed consent.

Exclusion criteria: e unexplained weight loss, presence of blood in the gastrointestinal system, anemia, use of systemic antibiotics, NSAIDs, or antipsychotics within 3 weeks before the study starts, pregnancy or lactation, a history of gastrointestinal neoplasia, suspicion of celiac disease, inflammatory bowel disease, endometriosis or pelvic inflammatory disease, abdominal surgery in the

2 years prior to the study (3 months for appendectomy or herniorrhaphy), allergy to any of the medications in the formula or using them in the last 3 months, BMI < 18, or not agreeing to signing of informed consent

N total at baseline: Intervention: 18 + 19

Control: 18

Important prognostic factors2:

Age ± SD:

I: 45 (9) + 45 (11)

C: 46 (5)

Sex:

I: 67 + 79% F

C: 56% F

Groups comparable at baseline for age, gender, BMI, Hb, glucose, IBS- type, IBS Qol, Bristol scale, abdominal pain VAS scale.

Describe intervention (treatment/procedure/test):

group 1 received 2 g of i3.1 probiotic formulation (effective dose 3 × 109

cfus) once daily for 6 weeks; group 2 received a capsule containing 60-mg alverine and 300-mg simethicone every 8 h (i.e., thrice daily), in combination with 2 g

of i3.1 probiotic formulation (effective dose 3 × 109

cfus) once daily, for 6 weeks;

The i3.1 probiotic formulation (ABBiotics SA, Barcelona, Spain) was a combination of 3 lactic acid bacteria: L. plantarum CECT 7484, L. plantarum CECT 7485, and

P. acidilactici CECT 7483

Describe control (treatment/procedur e/test):

group 3 received the placebo capsule every 8 h (i.e., thrice daily) for 6 weeks

Length of follow-up: 6 weeks

Loss-to-follow-up: Intervention:

N 0 (%)

Reasons (describe)

Control:

N 0 (%)

Reasons (describe)

Qol (IBS QoL 0-

100), abdominal

pain (VAS 0-10),

stool consistency (Bristol scale 1-7), adverse events

Andrese n, 2020

Type of study: RCT

Setting and country: primary and secondary care, Germany

Funding and conflicts of interest: Synformulas funded the study. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. PL has received reimbursement of travel expenses from

Falk, outside the submitted work. VA

Inclusion criteria: 18 years and older, criteria for IBS according to Rome III, abdominal pain >=4 on an 11 point numerical rating scale.

Exclusion criteria: inflammatory organic gastrointestinal diseases, systemic diseases , cancer, autoimmune diseases, diabetes, lactose intolerance, immune deficiency, abdominal surgery, hyperthyroidism, etc.

N total at baseline: Intervention: 221

Control: 222

Important prognostic factors2:

Age ± SD:

I: 40 (13)

C: 43 (14)

Sex:

has received speaker and consulting fees from Bayer, Falk and others, outside of the submitted work. JG has received consultant fees from Synformulas, outside of the submitted

work.

Describe intervention (treatment/procedure/test):

8 weeks 2 capsules 1x10 9 B fididum

I: 70% F

C: 69% F

Groups comparable at baseline for age, gender, height, weight, BMI, abdominal pain, IBD type.

Describe control (treatment/procedur e/test):

Maltodextrine

Length of follow-up: 12 weeks

Loss-to-follow-up: Intervention:

N 14 (%)

Reasons (describe) Adverse events Non compliance Other

Control:

N 13 (%)

Reasons (describe) Adverse events Non compliance Other

Pain response (abdominal pain 11 point numerical rating scale / IBS SSS), SF 12, global relief response

Stevenso n, 2019

Type of study: RCT

Setting and country:

?, South Africa

Funding and conflicts of interest: This study was funded in part by Nestle Nutrition Institute Africa (www.nnia.org) and the South African National

Research Foundation [gun number 2075266].

No potential conflict of interest was reported by the

authors.

Inclusion criteria: described in other article.

Exclusion criteria: described in another article

N total at baseline: Intervention: 19 + 16

Control: 9 + 8

Important prognostic factors2:

Age ± SD:

I: 52 (25-75)

C: 42-49 (32-72)

Sex: 51 of 52 female

Groups comparable at baseline? Yes , for age, BMI and duration of IBS symptoms.

Describe intervention (treatment/procedure/test):

The test product contained 5 × 109 colony forming units (CFU) of L. plantarum 299v

Describe control (treatment/procedur e/test):

micro-crystalline cellulose powder (mean content of cellulose per capsule 256 mg),

Length of follow-up: 12 weeks

Loss-to-follow-up: 0 Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

IBS symptoms with Francis Severity Score

Type of study: RCT

Setting and country: secondary care, Korea 

Funding and conflicts of interest:

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the High Value-Added Food Technology Development Program,

funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (316061-3).

The authors declare that they have no competing interests in association with this paper.

Inclusion criteria: Vietnamese individuals living in Korea aged between 19 and 60 years who

met the Rome III criteria [27] for the diagnosis of IBS were eligible to

participate.

Exclusion criteria: constipation- predominant

IBS (IBS-C), previous history of abdominal surgery except appendectomy and caesarian section, inflammatory bowel disease, and concurrent severe illnesses (cancer, cardiovascular, or pulmonary disease). In addition, patients who had used antipsychotics, antibiotics, and probiotics within 2 weeks

were also excluded.

N total at baseline: Intervention: 28

Control: 27

Important prognostic factors2:

Age ± SD:

I: 33 (27-39)

C: 33 (28-45)

Sex:

I: 64% F

C: 79% F

Groups comparable at baseline? The two groups were comparable for age, sex, body mass index (BMI), stool

form, IBS subtype, and abdominal pain.

Describe intervention (treatment/procedure/test):

The probiotic mixture (Foodis Lactobacillus, Ildong Group, Seoul, Korea) contained three strains of the Lactobacillus species, L. paracasei, L. salivarius, and

L. plantarum.

Describe control (treatment/procedur e/test):

Placebo capsules contained the excipient (olive oil and pine tree oil) only.

Length of follow-up: 4 weeks

Loss-to-follow-up: Intervention: 

N 2 (%)

Reasons (describe) withdrawn consent

Control:

N 3 (%)

Reasons (describe) withdrawn consent

Overall IBS symptom with SGA (0 (unchanged)-4 (completely relieved)),

abdominal pain with VAS (0 (none)-10 (very severe))

Type of study: RCT

Setting and country:

?, India. 

Funding and conflicts of interest: Tis study was fully funded by Unique Biotech Ltd., Hyderabad, India.

Each of the authors or their respective organizations were financially compensated by Unique Biotech Ltd for their contribution in the study.

R.S.M., J.J.A. and J.N.

are employed by Unique Biotech Ltd. which is a manufacturer of probiotics. They wish to state that the study was conducted independently with no intervention on their part during the duration of the study

Inclusion criteria: IBS, fulflling Rome III criteria i.e. abdominal discomfort/pain associated with two

or more of the following at least 25% of the time: improvement with 

defecation,

onset associated with change in frequency of stool/and or in the form (appearance) of stool // (a) patients of either sex in the age group of 18– 60 years, (b) fulflling Rome III criteria of IBS, (c) no evidence of infammatory, anatomic and metabolic or neoplastic process, (d) weekly, average worst abdominal pain score of ≥3.0 on 11 point scale,

5. average of less than 3 CSBMs per week (not due to the laxatives), and
6. able to provide informed consent

Exclusion criteria: (a) patients with Bristol stool scale score of 7 or 6 for

>25% of their bowel movements during

the 12 weeks before screening or, during the run-in period (except laxative induce efect). (b) disease that may affect bowel motility other than IBS, (c) presence of rectal bleeding, recent weight loss (>5 kg in the past month) or iron defciency anemia, (d) history of lactose intolerance and other malabsorption syndromes (e.g. fructose), (e) previous abdominal surgery and severe systemic diseases, (f) use of probiotic within 3 months of screening visit, (g) pregnant or breast-feeding or planning on becoming pregnant/women of child- bearing potential not using eff ective

contraception, (h) use of any 

antibiotics (e.g. neomycin, rifaximin) within 1 month of screening, (i) daily use of laxative within one

month of screening/current usage, or usage from the past 3 months, of narcotics

or other medications for IBS management (e.g. alosetron, tegaserod and lubiprostone).

N total at baseline: Intervention: 68

Control: 68

Important prognostic factors2:

Age ± SD:

I: 44

C: 42

Sex:

I: 23% F

C: 33% F

Groups comparable at baseline? Yes, for gender, age, height, weight.

Describe intervention (treatment/procedure/test):

B. coagulans Unique IS2

Describe control (treatment/procedur e/test):

Placebo

Length of follow-up: 8 weeks

Loss-to-follow-up: Intervention: 

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

In total 28; reasons: protocol deviations (11), violations (2), unavailable during follow up (15).

The primary efficacy outcomes were measured by assessing,

(a) pain intensity 

on 11-point numerical rating scale (NRS) and (b) frequency of CSBM/SBM. The

secondary efficacy outcomes

were measured by

1. severity of symptoms on 6- point Likert scale,
2. stool consistency on Bristol stool scale,
3. patient and physician global assessment. And adverse events.

Type of study: RCT

Setting and country: secondary care, Jordan.

Funding and conflicts of interest:

Funding not stated.

The authors declare that there is no conflict of interest regarding the publication of this paper.

Inclusion criteria: Patients included in the study were males

and females and the age between 18 and 70, diagnosed with IBS according to the Rome III criteria.

Exclusion criteria: Subjects were excluded if they had organic intestinal diseases, underwent

treatments that influence is, or taking any medication or herbals or 

probiotics.

N total at baseline: Intervention: 177

Control: 170

Important prognostic factors2:

Age ± SD: not in article

I:

C:

Sex: not in article

I: % M C: % M

Groups comparable at baseline? Yes, for IBS type.

Describe intervention (treatment/procedure/test):

four weeks two tablets of cerevisiae CNCM I-3856 (1000 mg) with a meal

Describe control (treatment/procedur e/test):

calcium gluconate 500 mg

Length of follow-up: 4 weeks

Loss-to-follow-up: Unknown

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

scores of abdominal pain/discomforts, bloating and flatulence, defecation difficulty, stool frequency, and stool consistency. A pain/discomfort

scored from 0 to 7 (Likert scale). Changes in stool frequency and consistency were followed daily using the Bristol Stool Scale from

(1) to (7).

Adverse events.

Al- Jassim, 2019

Type of study: RCT

Setting and country: secondary care?, Iraq.

Funding and conflicts of interest: There are no conflicts of interest of any sort. No information about funding.

Inclusion criteria: constipation- predominant IBS-C Rome III, and > 18 years of age

Exclusion criteria: Pregnant or breastfeeding

females, the presence of uncontrolled cardiovascular disease, diabetes

mellitus (type I or II), psychological conditions, renal or hepatic sickness, uncontrolled thyroid

disease, Parkinson’s disease, previous gastrointestinal surgery, allergy to ginger or S. cerevisiae (Brewer’s

yeast), and exclude patients taking medications that are frequently 

associated with constipation such as contraceptives, proton-pump inhibitors, beta-blockers, ACE inhibitors, calcium antagonists, statins,

diuretics, and barbiturates.

N total at baseline: Intervention: 15 + 15

Control: 15

Important prognostic factors2: No information in article.

Age ± SD:

I:

C:

Sex:

I: % M C: % M

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

500 mg Brewer’s yeast

Or

1g ginger

Brewer’s yeast (S. cerevisiae) 500 mg tablets of Adrien Gagnon Company were

used in the study. Ginger root powder (Zingiber officinale Roscoe,

Zingiberaceae) was capsulated in a dose of 1 g 

daily capsule provided

by simply organic company.

Describe control (treatment/procedur e/test):

The placebo capsules were prepared to contain brown sugar.

Length of follow-up: 20 days

Loss-to-follow-up: 0 Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

IBS severity scale (IBS-SS)

and visual analog scale of IBS (VAS- IBS) severity of pain, abdominal distention, and constipation (IBS- C)

subjects rated on a 0–100 scale, where 0 = none symptom and 100 = more severe symptom

Author and year

Reason for exclusion

Systematic reviews

Wen 2020

Wrong outcome

Sun 2020

More recent review available

Pratt 2020

Wrong (too specific) intervention

Li 2020

More recent review available

Gendi 2020

Background article, narrative

Asha 2020

More recent review available

Ohkusa 2019

Background article, narrative

Liang 2019

More recent review available

Dale 2019

More recent review available

Anbari 2019

Background article, narrative

Lacy 2018

Background article

Hungin 2018

Background article, narrative

Ford 2018

More recent review available

Domingo 2017

Foreign language

Zhang 2016

More recent review available

Tiequn 2015

Wrong (too specific) intervention

Didari 2015

Data not useful

Vitetta 2014

Background article

Ford 2014

More recent review available

Ortiz 2013

More recent review available

Ritchie 2012

Data not useful

Korpela 2012

Background article

Clarke 2012

Background article, narrative

Botschinsky 2010

More recent review available

Moayyedi 2010

More recent review available