Bacteroides
vesicles promote functional alterations in the gut microbiota composition
Authors: Shagaleeva Olga Yu. , Kashatnikova Daria A. , Kardonsky Dmitry A. , Efimov Boris A. , Ivanov Viktor A. , Smirnova Svetlana V. , Evsiev Suleiman S. , Zubkov Eugene A. , Abramova Olga V. , Zorkina Yana A. , Morozova Anna Y. , Vorobeva Elizaveta A. , Silantiev Artemiy S. , Kolesnikova Irina V. , Markelova Maria I. , Olekhnovich Evgenii I. , Morozov Maxim D. , Zoruk Polina Y. , Boldyreva Daria I. , Kazakova Victoriia D. , Vanyushkina Anna A. , Chaplin Andrei V. , Grigoryeva Tatiana V. , Zakharzhevskaya Natalya B. 
Published: September 2024

ABSTRACT

Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations in the gut microbiota composition.
Bacteroides fragilis
, which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate the inflammatory response and possibly alter the microbiota composition. In this study, we created a murine model of chronic sodium dextran sulfate (DSS)-induced intestinal colitis and treated it with
B. fragilis
OMVs. We monitored the efficiency of OMV therapy by determining the disease activity index (DAI) and performing histological examination (HE) of the intestine before and after vesicle exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compound composition in the animals’ stools by HS-GC/MS to assess the functional activity of the microbiota. We observed more effective intestinal repair after OMV treatment according to the DAI and HE. A metabolomic study also revealed changes in the functional activity of the microbiota, with a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS and the group treated with OMVs (DSS OMVs). We also observed a positive correlation of these metabolites with
Saccharibacteria
and
Acetivibrio
in the control group, whereas in the DSS group, there was a negative correlation of phenol and pentanoic acid with
Lactococcus
and
Romboutsia
. According to the metabolome and sequencing data, the microbiota composition of the DSS-treated OMV group was intermediate between that of the control and DSS groups. OMVs not only have an anti-inflammatory effect but also contribute to the recovery of the microbiota composition.

IMPORTANCE

Bacteroides fragilis
vesicles contain superficially localized polysaccharide A (PSA), which has unique immune-modulating properties. Isolated PSA can prevent chemically induced colitis in a murine model. Outer membrane vesicles (OMVs) also contain digestive enzymes and volatile metabolites that can complement the anti-inflammatory properties of PSA. OMVs showed high therapeutic activity against sodium dextran sulfate-induced colitis, as confirmed by histological assays. 16S rRNA sequencing of fecal samples from different inflammatory stages, supplemented with comprehensive metabolome analysis of volatile compounds conducted by HS-GC/MS, revealed structural and functional alterations in the microbiota composition under the influence of OMVs. Correlation analysis of the OMV-treated and untreated experimental animal groups revealed associations of phenol and pentanoic acid with
Lactococcus
,
Romboutsia
,
Saccharibacteria
, and
Acetivibrio
.