Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India: an open-label, single-arm pilot study

Abstract

Background: Probiotics have been shown to be useful for the treatment of many disease conditions. These beneficial effects are believed to be mediated by change in the composition of gut microbiota and modulation of the host immune responses. However, the available data on the effect of probiotics on these parameters are quite limited.

Methods: We studied the composition of fecal microbiota, using 16S rRNA sequencing, and host immune responses in peripheral blood (plasma cytokine levels, T cell subsets and in vitro cytokine production after stimulation with anti-CD3/CD28 antibody or lipopolysaccharide) in a group of 14 healthy women at three time-points - before and after administration of a probiotic preparation (a capsule of VSL#3, each containing 112.5 billion freeze-dried bacterial cells belonging to 8 species, twice a day for 4 weeks), and 4-weeks after discontinuation of the probiotic administration.

Results: There was no change in the abundance of various bacterial taxa as well as in the alpha diversity of gut microbiota following administration of the probiotic, or following its discontinuation. Probiotic administration led to a reduction in the relative frequency of circulating Th17 cells, and in vitro production of cytokines in whole-blood cultures in response to lipopolysaccharide stimulation. However, it had no effect on the relative frequencies of Th1, Th2 and T regulatory cells among circulating peripheral blood mononuclear cells, on plasma cytokine levels and on in vitro production of cytokines by T cells.

Conclusions: We found that VSL#3 administration did not lead to any changes in gut flora, but led to a reduction in the frequency of Th17 cells and in the production of pro-inflammatory cytokine on lipopolysaccharide stimulation. These findings suggest that the beneficial anti-inflammatory effect of this preparation in patients with autoimmune and allergic disorders may be related to reduced production of monocyte-derived cytokines rather than to changes in the composition of gut microbiota.

Trial registration: NCT03330678 , Date of registration 30th October 2017. Retrospectively registered.

Keywords: Gut microbiome; Healthy women; Immune response; Probiotic; VSL#3.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by Ethics Committee of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow. Each participant provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

CONSORT flow diagram

Fig. 2

Abundances of various bacterial families (a) and genera (b) in fecal microbiota from healthy women before (blue) and after (red) four weeks of probiotic administration. Data are shown using box-plots and percent values on a log10 scale. The ends of boxes represent 25th to 75th centiles, and any dots to the left or right of the boxes indicate outliers

Fig. 3

Abundances of bacterial families (a) and genera (b) in fecal microbiota from healthy women after four weeks of probiotic administration (red) and 4-weeks after discontinuation of probiotic administration (green). Data are shown using box-plots and percent values on a log10 scale. The ends of boxes represent 25th to 75th centiles, and any dots to the left or right of the boxes indicate outliers

Fig. 4

Frequencies of Th1 (a), Th2 (b), Treg (c) and Th17 cells (d) in whole blood cultures from healthy women (n = 14) at baseline, after 4-weeks of probiotic administration and 4-weeks after discontinuation of probiotic administration (8 wk) by flow cytometry (Mann-Whitney U test)

Fig. 5

Estimation of levels of cytokines (pg/ml): IL-10 (a), IL-6 (b) and TNF (c), predominantly produced by monocytes on LPS stimulation of whole blood in culture supernatant of healthy women (n = 14). The estimation was done at three time-points; baseline, 4-weeks of probiotic administration and 4-weeks after discontinuation of probiotics by BD Cytometric Bead Array (Mann-Whitney U test)