Prevention of TNBS-induced colitis by different Lactobacillus and Bifidobacterium strains is associated with an expansion of gammadeltaT and regulatory T cells of intestinal intraepithelial lymphocytes.
BACKGROUND
Probiotics may protect against inflammatory bowel disease through regulation of lamina propria lymphocytes (LPLs) function. Data are lacking on possible involvement of intraepithelial lymphocytes (IELs). The aim of this study was to investigate whether different probiotic mixtures prevented gut inflammatory disease and the role of both IELs and LPLs.


METHODS
BALB/c mice received 2 probiotic mixtures orally for 3 weeks, as Mix1 (Lactobacillus acidophilus and Bifidobacterium longum), or Mix2 (Lactobacillus plantarum, Streptococcus thermophilus, and Bifidobacterium animalis subsp. lactis). Colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS). Probiotics in stools were analyzed by real-time polymerase chain reaction (PCR). Colon subpopulations of IELs and LPLs were assayed by flow cytometry. Serum cytokines were measured by cytometric bead array (CBA).


RESULTS
All probiotics colonized the intestine. The 2 mixtures prevented the TNBS-induced intestinal damage, and Mix1 was the most effective. The Mix1 protection was associated with a reduction in CD4(+) cells of IELs and LPLs, an increase in gammadeltaT cells of IELs, and a decrease in gammadeltaT cells of LPLs. An expansion of T regulatory (Treg) cells of IELs was induced by Mix1 and Mix2. Both probiotic mixtures inhibited tumor necrosis factor (TNF)-alpha and monocyte chemotactic protein (MCP)-1 production and upregulated interleukin (IL)-10. In addition, Mix1 prevented the TNBS-induced increase of IL-12 and interferon (IFN)-gamma.


CONCLUSIONS
The 2 probiotic mixtures were able to prevent the TNBS-induced colitis; the L. acidophilus and B. longum mixture was the most effective. Other than an involvement of LPLs, our results report a novel importance of the IELs population in probiotic protection.
Roselli
Marianna
M
Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, Roma, Italy.
Finamore
Alberto
A
Nuccitelli
Silvia
S
Carnevali
Paola
P
Brigidi
Patrizia
P
Vitali
Beatrice
B
Nobili
Fabio
F
Rami
Rita
R
Garaguso
Ivana
I
Mengheri
Elena
E
D000818:Animals; D001644:Bifidobacterium; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D007778:Lactobacillus; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D019936:Probiotics / Q000627:therapeutic use*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014302:Trinitrobenzenesulfonic Acid