SUNDAY-79 Consumption of a Novel Probiotic Leads to Beneficial Structural Functional Changes in the Gut Bacteriome and Mycobiome of Human Volunteers Schrom K1, Retuerto M1,2, Salem I1,2, Cousineau, S3, Hartman L3, Barth C3, Bebek G4, Hawser S5, Sahm D6, and Ghannoum, MA1,2 1 2 3 Department of Dermatology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Center for Medical Mycology, Fermentation Phone: 216.844.5728 4 5 Festival, Santa Monica, California, Department of Nutrition and Biological Sciences, Case Western Reserve University, Cleveland, OH, IHMA Europe Sàrl, Monthey, Email: [email protected] Switzerland, 6IHMA, Inc., Schaumburg, IL

Abstract Results Results

The role of gastrointestinal fungal-bacterial interactions in Crohn’s disease (CD) has been virtually unstudied; but in a recent study of ours, a positive correlation was observed. E. coli, S. marcescens, and C. tropicalis were relatively elevated in CD patients. Together, these microbes formed pathogenic biofilms capable of inducing inflammation. Therefore, we posited CD patients could benefit from a novel probiotic formulation that antagonized pathogenic microbes • Levels of tended to increase in abundance while while supporting beneficial ones. Inter- correlation analysis allowed us to develop such a probiotic; it contained S. boulardii, L. acidophilus, L. rhamnosus, B. breve, and amylase. Once developed, in vitro and in vivo studies were performed. Here we report the results of our investigation into how our Zygomycota (p < 0.001) abundance was normalized compared to probiotic modulates the microbiota of healthy subjects. baseline, in our subjects post-dosing. Our novel, enteric-coated probiotic (provided by BIOHM Health, Cleveland, OH) was administered to healthy volunteers over 4-weeks. Stool samples from our subjects (n = 44) were analyzed before and after probiotic administration with the Ion-Torrent sequencing platform. The bacteriome profiles of our subjects • Candida abundance levels were significantly higher (p <0.013) pre- were subsequently compared to subjects from the Normal Human Project (NHMP). While that of the mycobiome was compared to data captured from control subjects studied at Case Western Reserve University’s Center for Medical Mycology. dosing but significantly lower (p <0.013) post-dosing. Our subjects had lower levels of Ascomycota and higher levels of Zygomycota fungal phyla prior to probiotic administration; however, normal levels, mirroring • C. albicans levels were significantly higher (p <0.013) pre-dosing, but NHMP subjects, were reached post dosing (P<0.01). The Candida genus and the specific species, C. albicans, were higher in our subjects (P<0.013) prior to probiotic administration and the Candida genus level was significantly lower (P<0.013) after; C. albicans levels also tended to be lower. Additionally, prior to tended to be lower post-dosing. administration, levels of the Firmicutes bacterial phylum were higher (P<0.001) in our subjects but decreased to normal NHMP levels following probiotic administration. • Firmicutes levels were higher (p <0.001) pre-dosing and were In conclusion, after administration of the novel probiotic, our subjects attained levels of Firmicutes, Ascomycota, and Zygomycota consistent with subjects normalized post-dosing. from the NHMP. Additionally, the overabundance of Candida; and specifically, C. albicans, were reduced to normal levels. These findings suggest that use of this new probiotic leads to structural and functional changes in the gut bacteriome and mycobiome that could be beneficial to balancing the gut microbiome.

Objective Conclusions

Determine the effect a novel probiotic mixture on the human bacteriome and • The study data demonstrated that BIOHM significantly mycobiome structure. rebalanced major organisms of the gut microbiome. • BIOHM may have utility in addressing gut imbalance. Figure 1. Phyla Level Profile of the Mycobiome Community before and after 4 weeks of daily Figure 2. Profile of the Bacterial Community before and after 4 weeks of daily BIOHM BIOHM dosing Further studies are warranted. Introduction dosing.

• In Crohn’s disease patients(CD), E. coli, S. marcescens, and C. tropicalis are higher in abundance and positively-correlated. Acknowledgement • They are capable in forming mixed-species, inflammation-inducing, pathogenic biofilms (1). Supported by Biohm in which MAG is the chief scientific officer. • We hypothesized, therefore, that a carefully designed probiotic could disrupt these pathogenic biofilms and rebalance the . • Inter-kingdom correlation analysis identified novel probiotic strains capable of inhibiting pathogenic microbes while supporting beneficial gut References flora. • The aim of this study was to evaluate whether the use of this novel probiotic could impact the microbiota of healthy volunteers. 1. Hoarau G, Mukherjee PK, Gower-Rousseau C, et al. Bacteriome and Mycobiome Interactions Underscore Microbial in Familial Crohn's Disease. MBio. 2016; 7(5). pii: e01250-16. doi: 10.1128/mBio.01250-16.

Methods

• Oral, enteric-coated probiotic mixture (BIOHM) consisted of S. boulardii, L. acidophilus, L. rhamnosus,& B. breve plus amylase Figure 3. Candida levels before and after 4 weeks of daily BIOHM dosing Figure 4. Firmicutes levels before and after 4 weeks of daily BIOHM dosing • Administered to healthy volunteers (n=44) over 4 weeks • Stool samples were collected at baseline and following probiotic use and were analyzed with Ion-Torrent sequence technology • Microbiome profiles were compared pre- and post-probiotic use