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Table 2 Novel certain human clinical trials on live biotherapeutic products (LBPs) in gut brain axis related conditions

From: Recent developments in the probiotics as live biotherapeutic products (LBPs) as modulators of gut brain axis related neurological conditions

Gut brain axis related conditions

LBPs

Subjects

Dose

Intervention duration

Results

Reference

Autism

Lactobacillus Acidophilus

Lacticaseibacillus rhamnosus

Bifidobacteria longum

ASD cases

(n:30)

%63.3 male

Controls

(n:30, matched gender and age)

5–9 years old

Prospective, open-label, case–control study

Probiotic mixture each gram contains 100 × 106 CFU

Obtainable as a powder to be diluted in water Once-daily 5 g/day

3 months

Pre-intervention Bifidobacteria levels less in ASD feces were lower than in the control group

Bifidobacteria and Lactobacillus levels increased after probiotic intervention in in ASD children

Autism Treatment Evaluation Checklist (ATEC) overall scores decreased. It demonstrates that the severity of ASD symptoms decreased

Overall GI symptom severity was reduced (constipation, gas, stool consistency, and abdominal pain)

[63]

Autism

Lactiplantibacillus Plantarum PS128

Aged 7–15 years

n: 71,

(%100 male)

(E: 36, C: 35)

Randomized, placebo-controlled, double-blind study

3 × 1010 CFU with microcrystalline cellulose

Placebo: Microcrystalline cellulose

1 capsule Daily

4 weeks

Opposition/defience behaviors improved after treatment wirh Lactiplantibacillus plantarum PS128

Observing that younger children (7–12 years old) benefit more than older children (13–15 years old), the intervention appears to have an age-related effect

[61]

Autism

Visbiome®

(formerly VSL#3)

Four strains of Lactobacilli

Lacticaseibacillus casei,

Lactobacillus delbrueckii subsp. bulgaricus,

Lactiplantibacillus plantarum,

Lactobacillus acidophilus

Three strains of Bifidobacteria Bifidobacterium infantis Bifidobacterium breve

Bifidobacterium longum

One strain of Streptococcus Thermophiles

Aged 3–12 years

N:13,

(%60 male)

(Group 1:6, Group 2: 4)

Group 1: 8-week probiotic + 3-week washout + 8-week placebo

Group 2: 8-week placebo + 3-week washout + 8-week probiotic

Randomised, cross-over pilot, placebo-controlled study

90 × 1010 CFU/packet

Dose: 1/2 packet Twice a day (weeks1–4)

Option to increase to 1packet twice a day at (week 5–15)

Placebo: matched but ingredients not stated

19 weeks

(8 weeks, 3-week washout, 8 weeks)

GI symptoms that were aimed at the parents improved significantly

There was no change in the gut microbiome diversity or strain family-level composition

Probiotics have a clear transport effect

The probiotic effects lasted throughtout the entire 3- washout period

[62]

Autism

Visbiome®

(formerly VSL#3)

Four strains of Lactobacilli

Lacticaseibacillus casei,

Lactiplantibacillus plantarum,

Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus acidophilus,

Three strains of Bifidobacterium longum Bifidobacteria

Bifidobacterium breve Bifidobacterium infantis

One strain ofStreptococcus Thermophiles

18–72 months (4.2 years)

(%84 male)

n: 63

ASD treatment

(n: 31)

ASD Control

(n: 32)

Placebo controlled, randomised trial

450 billion CFU were present in each packet

2 packets/day in the first month of treatment and

1 packet/day in the following 5 months

Placebo: 4.4 g of maltose + silicondioxide

6 months

There is no significant difference in the Total Autism Diagnostic Observation Schedule – Calibrated Severity Score (ADOS-CSS score)

Plasma biomarkers (IL-6, TFN-α) and faecal calprotectin didn’t differ significantly

Analysis of subgroups

There was no GI group (n = 46)

Total ASD severity scores ADOS and Social-Affect ADOS scores decreased

GI group (n = 17)

Between baseline and 6 months, the probiotic group exhibited a significant difference from the control group

Reduced total GI severity, stool odor and flatulence

Improved adaptive skills (Repetitive, Domestic, Coping skills)

Scores from sensory profiles were normalized (improvements in 87 percent of probiotic group vs 28 percent of placebo group)

[64]

Alzheimer Disease

Lactococcus lactis W19

Lactobacillus acidophilus

W22

Lacticaseibacillus casei

W56

Bifidobacterium lactis W52

Lacticaseibacillus paracasei

W20

Lactiplantibacillus plantarum W62, Bifidobacterium lactis

W51

Bifidobacterium bifidum W23 Ligilactobacillus salivarius W24

Twenty (11 males, 9 females, aged 76.7 ± 9.6 years) Alzheimer’s disease patients

Omnibiotic Stress

Repair (Allergosan, Graz, Austria)

28 days

The serum levels of kynurenine significantly increase as a result of probiotic supplementation

BDNF levels did not change before or after taking probiotic supplements for 4 weeks

After 4 weeks of probiotic administration, the RNA content of the fecal bacteria strain Faecalibacterium prausnitzii considerably increased, whereas the contents of Clostridium cluster I and Akkermansia muciniphila remained unaltered

Zonulin concentrations dropped at the two time points just before and after taking probiotic supplements for four weeks

[65]

Alzheimer Disease

Limosilactobacillus fermentum

Lactiplantibacillus plantarum Bifidobacterium lactis

or

Lactobacillus acidophilus

Bifidobacterium longum Bifidobacterium bifidum

Forty-eight alzheimer disease individuals,

with no comorbidities and aged 65–90 years

Control (n: 23)

Probiotic (n: 25)

Total dosage of 3 × 109 CFU

(2 capsules once a day)

12 weeks

There have been no significant changed Test Your Memory, total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA), IL-6, TNF-α, IL-10, nitric oxide (NO), 8-hydroxy-2' -deoxyguanosine (8-OHdG) levels

[66]

Alzheimer Disease

Bifidobacterium breve A1 (MCC1274)

50–79 years 80 healty individuals with mild cognitive impairment (MCI)

Probiotic group (n: 39)

Placebo group (n: 40)

A Randomized, Double-Blind, Placebo-Controlled Trial

2 × 1010 CFU

16 weeks

When compared with placebo in the probiotic group;

Immediate memory, visuospatial/constructional score, delayed memory and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were significantly improved

[67]

Alzheimer Disease

Lacticaseibacillus rhamnosus GG

52–75 year old adults were enrolled

Probiotic group (n: 77)

Placebo group (n: 68)

Culturelle Vegetarian Capsules containing a 10 billion CFU blend

two capsules daily

90 days

In middle-aged and older persons with cognitive impairment, supplementation was associated with enhanced cognitive function

[68]

Parkinson Disease

Lactobacillus acidophilus Bifidobacterium bifidum, Limosilactobacillus reuteri

Limosilactobacillus fermentum

Aged 50–90 yaers, had a Parkinson Disease diagnosis

Probiotic (n: 30)

Placebo (n: 30)

Each bacteria 2 × 109 CFU/g

12 weeks

In probiotic group;

The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was reduced

Serum hs-CRP, MDA, insülin, HOMA-IR, triglyceride and very low-density lipoprotein-cholesterol (VLDL-C) levels were reduced and GSH levels were increased

[69]

Parkinson Disease

Lactobacillus Acidophilus

Limosilactobacillus reuteri

Lactobacillus gasseri Lacticaseibacillus rhamnosus,

Bifidobacterium bifidum, Bifidobacterium longum,

Enterococcus faecalis, Enterococcus

faecium

Aged 40 years or older, had a Parkinson Disease diagnosis individuals

Probiotic (n: 34)

Placebo (n: 38)

Each probiotic capsule contained 10 billion CFU

4 weeks

The average number of spontaneous bowel movements (SBM) per week was increased

The groups didn’t differ significantly in ters of fecal calprotectin changes from baseline to the end of the treatment

Changes in stool consistency, constipation severity score, and quality of life related to constipation all showed significant improvements in the intervention group

[70]

Parkinson Disease

Lactiplantibacillus plantarum PS128 (PS128)

Aged 40–80 years had a Parkinson Disease diagnosis

8 female/17 male

Two capsules Daily (30 billion CFU per capsule)

12 weeks

Administration of PS128 was any significant impact on rigidity, tremor, PIGD subscores, or Mhys

Significantly decreased Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores and akinesia subscores

PS128 use significantly decreased plasma myeloperoxidase levels and the urinary creatinine levels

When comparing the scores of individuals with Parkinson’s Disease Questionnaire (PDQ-39), the single index score, mobility, activities of daily living, stigma and cognition significantly decreased after the 12-week supplementation

[71]