Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 28, 2012; 18(16): 1875-1883
Published online Apr 28, 2012. doi: 10.3748/wjg.v18.i16.1875
Probiotic metabolites from Bacillus coagulans GanedenBC30TM support maturation of antigen-presenting cells in vitro
Kathleen F Benson, Kimberlee A Redman, Steve G Carter, David Keller, Sean Farmer, John R Endres, Gitte S Jensen
Kathleen F Benson, Kimberlee A Redman, Steve G Carter, Gitte S Jensen, NIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, United States
David Keller, Sean Farmer, Ganeden Biotech, 5915 Landerbrook Drive, Mayfield Heights, OH 44124, United States
John R Endres, AIBMR Life Sciences, 4117 S Meridian, Puyallup, WA 98373, United States
Author contributions: Jensen GS, Keller D, Farmer S, and Endres JR conceived the idea to test and compare the bioactivity of bacterial cell walls and metabolites; Jensen GS and Benson KF planned the procedure for generating the two test fractions; Jensen GS and Benson KF designed the study and coordinated the lab work and data analysis; Benson KF performed the production of the GBC30 fractions; Benson KF, Redman KA, and Carter SG performed the in vitro testing, analysis, and contributed to the writing of the manuscript; Benson KF did the statistical analysis; Benson KF, Jensen GS, Keller D, Farmer S and Endres JR finalized the manuscript writing.
Supported by A Research Sponsorship from Ganeden Biotech, Ohio, United States
Correspondence to: Kathleen F Benson, PhD, NIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, United States. kathy@nislabs.com
Telephone: +1-541-8840112 Fax: +1-403-4415236
Received: July 30, 2011
Revised: December 20, 2011
Accepted: April 1, 2012
Published online: April 28, 2012
Abstract

AIM: To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.

METHODS: Ganeden Bacillus coagulans 30 (GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite (MET) fraction. A second fraction was made to generate a crude cell-wall-enriched fraction, by centrifugation and lysis, followed by washing. A preparation of MET was subjected to size exclusion centrifugation, generating three fractions: < 3 kDa, 3-30 kDa, and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell (PBMC) as a source of antigen-presenting mononuclear phagocytes. The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14, CD16, CD80 and CD86 and analyzed by flow cytometry.

RESULTS: Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes. The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells, and this property was associated with the high molecular weight metabolite fraction. Changes were also seen for the dendritic cell maturation markers CD80 and CD86. On CD14dim cells, an increase in both CD80 and CD86 expression was seen, in contrast to a selective increase in CD86 expression on CD14bright cells. The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation. The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.

CONCLUSION: The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells, important for immunological decision-making.

Keywords: Mononuclear phagocytes; Dendritic cell maturation; Co-stimulatory molecules; Antigen-presentation; Probiotics; Metabolites