Effect of Galacto-Oligosaccharides supplementation on amoxicillin-treated gut microbiota from healthy adults : a proof of principal study

Prebiotics are thought to be a potential means to prevent antibiotic-associated
diarrhoea because of their ability to stimulate beneficial bacteria. In-vitro
results showed a promising recovery of Bifidobacteria combined with an increase
of Short Chain Fatty Acids (SCFA) upon Galacto-oligosaccharides (GOS)
supplementation to amoxicillin-treated microbiota. As the microbiota is
nowadays considered as a key factor in human health, a further understanding of
the gut microbiota functioning in-vivo is essential. This understanding of the
use of specific prebiotics may possibly be beneficial in the prevention or
recovery of antibiotic-disturbed microbiota. As the effect of GOS
supplementation in healthy adults receiving amoxicillin have never been tested
in-vivo, we propose the current study as a proof of principle. The main aim of
the study is to investigate changes in microbiota composition and -activity of
persons having received antibiotics with/without GOS as compared to the
baseline rather than investigating the occurrence of diarrhoea

To explore whether the promising effects of GOS supplementation on the
composition and activity of gut microbiota from healthy adults as found by
in-vitro, can also be observed in-vivo.

Double blind randomized parallel intervention study comprising two weeks
intervention and two weeks of follow up. Fecal samples will be collected on 8
occasions : at screening, day 0, day 2, day 5, day 8, day 12 day 19 and day 26.
Fecal samples at day 0 will be used to perform the in-vitro parallel study.

All subjects will receive amoxicillin (375 mg 3x per day) for 5 days. Group 1
receives a drink with GOS (2,5 g 3x per day) and group 2 receives a drink with
placebo (Maltodextrine 2,5 g 3x per day) simultaneously to the antibiotic for 5
days and after the antibiotic treatment for another 7 days, 12 days in total.
The intervention products should be consumed at breakfast/lunch/dinner.

This intervention is non-therapeutic to the subjects. The risk associated with
participation and the burden are considered low but present. At screening, an
inclusion questionnaire is filled out and height and weight are measured.
Subject still have the opportunity to drop-out before starting the study.
During the study, antibiotic treatment and GOS or placebo supplemented to a
drink are taken for 5 and 12 days, respectively, at home during breakfast,
lunch and dinner. Eight faecal samples will be collected and will be picked up
at home by the researchers. Delivery of faecal samples can be 1 day after the
indicated date. After the treatment, the subjects will be followed up for two
weeks to check whether they feel as healthy as before the study.
Amoxicillin is a marketed drug commonly used for the treatment of infections.
Like all medicines, the study drug may cause side effects, but side effects are
usually mild and transient in nature, nausea and diarrhoea being the most
common ones. The risk for serious adverse events is considered to be lower in
healthy adults as their microbiota is mature/diverse and stable as compared to
infant or elderly. The healthy volunteers keep a diary and are being monitored
at each required faecal donation for adverse events. Subjects will be withdrawn
from the study when diarrhoea is occurring and be followed by a general
practitioner.
Although subjecting healthy people to antibiotics is considered to be undesired
due to possible side effects, we felt that we did not have another choice. The
option to recruit adults needing antibiotic treatment due to a minor infection
was not optimal as we considered the lack of a baseline observation and faecal
sample, the diversity of treatment regarding dose and duration as prescribed by
the practitioner and the rush in getting started (no real time to inform the
volunteer properly) as limiting factors to have a good, representative and
volunteer-friendly study. In addition, using healthy volunteers in antibiotic
studies using amoxicillin has been reported before. Finally, risk for diarrhoea
that exist for healthy adult receiving amoxicillin treatment are defined as
*nuisance diarrhoea*, which is a frequent loose and watery stools with no other
complications. Risk for colitis, which is a potential source of serious
progressive disease, is rare (< 0,01%).
Prebiotic GOS is known to be safe and food-grade. Possible side-effects may be
bloating and flatulence but these effects are harmless and not likely to happen
with 7.5g/day GOS intake.