Effects of Probiotic, Antibiotic or Combination on Intestinal Microbiota in Healthy Humans

7 Apr, 21

Introduction

Antibiotics disrupt normal gut microorganisms and this dysbiosis impairs “colonization resistance” making the subject more vulnerable to opportunistic overgrowth within the microbiota.

Aim

To examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms in healthy humans.

Patient Profile

Healthy subjects with mean age of 30 years

Methods

Single-center, open-label, randomized controlled trial in healthy volunteers

Participants gave stool samples and completed gastro-intestinal symptom questionnaires
Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing

Endpoint

The main endpoint was the change from baseline in the composition of the gut microbiota
Other endpoints were Gastrointestinal Symptom Rating Scale (GSRS) scores and bowel movements characteristics recorded in a Daily Stool Log (frequency, consistency)

Results

Significant microbiota changes were noted in the AC alone group during antibiotic treatment
AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter.
- Amoxicillin-Clavulanate was administered in conjunction with S. boulardii the increase in Escherichia prevalence was substantially less (0.037%, not statistically significant).
- After treatment the prevalence of Escherichia fell to baseline in both the antibiotic alone and the antibiotic with S. boulardii groups
Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotic therapy
In SB group, no significant changes in bacterial genera were noted
Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhoea scores
Control subjects had a stable microbiota throughout the study period

The group of subjects treated by antibiotics alone (AC group) showed worsening of the gastrointestinal symptoms during the treatment period (Days 0 to 7) (Table1)

Table 1: GSRS total scores by treatment group and study period

Gastrointestinal Symptom Rating Scale – Scores	Group 1 Sb (N = 13)	Group 2 AC (N D 12)	Group 3 Sb C AC (N = 12)	Group 4 Control (N =12)	Total (N = 49)
Gastrointestinal symptoms total score D-7 to D0
N	13	12	12	0	37
Mean	18.7	18.7	17.3	NA	18.2
Gastrointestinal symptoms total score D0 to D7
N	13	12	12	12	49
Mean	23.2		18.1	19.3
Gastrointestinal symptoms total score D7 to D14
N	12	11	12	12	47
Mean	19.3	20.3	16.8	16.4	18.1
Gastrointestinal symptoms total score D14 to D21
N	12	11	12	12	47
Mean	19.3	18.4	16.5	15.8

All of the Gastrointestinal Symptom Rating Scale - Scores (GSRS) subscores from the SBCAC group were numerically lower than those from the SB alone group and from the AC group
The most substantial and statistically significant differences were related to the “diarrhea-GSRS sub-score”
- The mean diarrhea- GSRS sub-score was statistically increased in the AC group on Day 7 compared with Day 0 (difference: 3.83 +1.10, p = 0.001)
- In inter-group comparison, the mean diarrhea- GSRS sub-score for the AC group at day 7 was significantly elevated compared with the SBCAC group (difference: 3.92 + 1.37 (p= 0.01)

14 of the 49 subjects (28.6%) reported adverse events (AEs) most of which were mild to moderate and related to gastrointestinal disorders including bloating, loose bowel movements and flatulence.
- S boulardii + AC group showed fewer AEs and tolerated the study regimen better than those receiving the AC alone

Conclusion

Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera.
S. boulardii administered together with amoxicillin-clavulanate, microbiota changes, including Escherichia overgrowth, were lessened and antibiotic-associated diarrhea was prevented.
S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea

Reference

Gut Microbes. 2017 Jan 2;8(1):17-32.