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. 2010 Oct 19;107(42):18132-7.
doi: 10.1073/pnas.1011737107. Epub 2010 Oct 4.

Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes

Patrick Veiga  1 , Carey Ann Gallini, Chloé Beal, Monia Michaud, Mary L Delaney, Andrea DuBois, Artem Khlebnikov, Johan E T van Hylckama Vlieg, Shivesh Punit, Jonathan N Glickman, Andrew Onderdonk, Laurie H Glimcher, Wendy S Garrett
Affiliations

Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes

Patrick Veiga et al. Proc Natl Acad Sci U S A. .

Erratum in

  • Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21943

Abstract

Intestinal health requires the coexistence of eukaryotic self with the gut microbiota and dysregulated host-microbial interactions can result in intestinal inflammation. Here, we show that colitis improved in T-bet(-/-)Rag2(-/-) mice that consumed a fermented milk product containing Bifidobacterium animalis subsp. lactis DN-173 010 strain. A decrease in cecal pH and alterations in short chain fatty acid profiles occurred with consumption, and there were concomitant increases in the abundance of select lactate-consuming and butyrate-producing bacteria. These metabolic shifts created a nonpermissive environment for the Enterobacteriaceae recently identified as colitogenic in a T-bet(-/-)Rag2(-/-) ulcerative colitis mouse model. In addition, 16S rRNA-based analysis of the T-bet(-/-)Rag2(-/-) fecal microbiota suggest that the structure of the endogenous gut microbiota played a key role in shaping the host response to the bacterial strains studied herein. We have identified features of the gut microbiota, at the membership and functional level, associated with response to this B. lactis-containing fermented milk product, and therefore this model provides a framework for evaluating and optimizing probiotic-based functional foods.

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Conflict of interest statement

Conflict of interest statement: L.H.G. is a member of the Board of Directors of and holds equity in the Bristol Myers Squibb Corporation. P.V., C.B., A.K., and J.E.T.v.H.V. are employees of and hold equity in Groupe Danone.

Figures

Fig. 1.
Fig. 1.
BFMP improves T-bet−/−Rag2−/−colitis and requires live B. lactis. (A) T-bet−/−Rag2−/− mice consumed a BFMP (n = 18), MP (n = 19), or sham (n = 7) daily from 4 to 8 wk of age. (B) T-bet−/−Rag2−/− mice consumed the BFMP (n = 13), MP (n = 11), or sham (n = 13) daily from 12 to 16 wk of age. (C) T-bet−/−Rag2−/− mice consumed BFMP (n = 17), irradiated and sterile BFMP (n = 19), or sham (n = 6). Colitis scores (y axis). Each circle shows data from one mouse. Horizontal bars represent mean. P values, Mann–Whitney test.
Fig. 2.
Fig. 2.
Consumption of B. lactis-containing fermented milk product creates a nonpermissive environment for colitogenic T-bet−/−Rag2−/− Enterobacteriaceae. (A) qPCR using primers targeting Enterobacteriaceae. Pre- and postconsumption levels for MP (●) or BFMP (○) (y axis), expressed as log10(equivalent cells/g feces). Each circle indicates data from one mouse; horizontal bars show the mean. P values, Mann–Whitney test. (B) Quantitative fecal culture pre- and post- BFMP and MP (as in A). Colony counts for K. pneumoniae (○) and P. mirabilis (□); detection limit is shown. Each symbol shows data from one mouse; bars show the mean; P values, where significant, are shown. (C) Cecal pH for T-bet−/−Rag2−/− that consumed BFMP, MP, or sham and for sham Rag2−/− mice. Mean values from three independent experiments are shown (n = 5 mice/sample). Error bars represent SD. (D) qPCR and RT-qPCR of fecal samples pre- and postconsumption of MP or BFMP. Data expressed as log10(equivalent cells/g feces).
Fig. 3.
Fig. 3.
Altered SCFA profiles and increased levels of specific lactate-consuming, butyrate-producing bacteria define a nonpermissive environment for colitogenic T-bet−/−Rag2−/− Enterobacteriaceae. (A) Volatile and nonvolatile SCFA levels of cecal contents for BFMP, MP, and sham T-bet−/−Rag2−/− mice and sham Rag2−/− mice. Bars show mean values from three independent experiments (n = 5 mice/ sample). Error bars indicate standard deviation. (B) qPCR and RT-qPCR using primers targeting the indicated bacteria genera or species. Pre- and postconsumption levels for MP (●) or BFMP (○) shown along the y axis (log10(equivalent cells/g feces)). Each circle indicates data from a single mouse. Horizontal bars show the mean. P values were calculated by Mann-Whitney test or Wilcoxon signed-rank test. (C) Growth kinetics of T-bet−/−Rag2−/−-derived strains of K. pneumoniae and P. mirabilis over a 3-h time course in media with pH and SCFA concentration adjusted to model cecal contents of T-bet−/−Rag2−/− mice that consumed BFMP or MP.
Fig. 4.
Fig. 4.
Structure of gut microbiota influences response to B. lactis-containing fermented milk product. (A) Distribution of family-level phylotypes in T-bet−/−Rag2−/− and Rag2−/− fecal microbiota at 4 wk of age (preconsumption). Percent relative abundance is plotted. (B) Bifidobacterium levels (qPCR) from 4-wk-old T-bet−/−Rag2−/− (n = 20) (○) and Rag2−/− (n = 10) (●) fecal samples. (C) B. lactis counts (log10CFU/g feces) (y axis) of sufficient quantity from mice in Fig. 1. Mice grouped by product administered and colitis score (x axis). Each circle represents a single mouse; horizontal bars show the mean. (D) Family-level hierarchical clustering analysis of T-bet−/−Rag2−/− fecal microbial communities before product consumption. Each sample is labeled corresponding to its relative abundance data in A, and colitis scores postconsumption are heat map color coded based on tertile distribution. (E) Postconsumption recovery levels of BFMP strains are heat map color coded based on tertile distribution for the corresponding sample in A and D.
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