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P026 Microbial Diversity is affected by Cognitive Behavioral and Mindfulness-Based Stress Reduction and accompanied by an Inflammatory Response in Patients with Crohn’s Disease

Ilan, K.(1);Motro, Y.(2);Nemirovsky, A.(2);Lerner, L.(3);Schwartz, D.(4);Goren, G.(5);Sergienko, R.(6);Greenberg, D.(7);Slonim-Nevo , V.(5);Sarid, O.(5);Friger, M.(6);Regev, S.(5);Odes, S..(8);Moran-Gilad , J.(9);Monsonego, A.(10);

(1)Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- Faculty of Health Sciences, Beer Sheva, Israel;(2)Faculty of Health Sciences- Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics, Beer Sheva, Israel;(3)Faculty of Health Sciences- Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- and The National Institute of Biotechnology in the Negev- Zlotowski Neuroscience Center- and Regenerative Medicine and Stem Cell Research Center, Beer Sheva, Israel;(4)Faculty of Health Sciences- Ben-Gurion University of the Negev- and Soroka Medical Center, Gastroenterology & Hepatology, Beer Sheva, Israel;(5)Ben-Gurion University of the Negev, Spitzer Department of Social Work, Beer Sheva, Israel;(6)Faculty of Health Sciences- Ben-Gurion University of the Negev, Department of Public Health, Beer Sheva, Israel;(7)Faculty of Health Sciences- Ben-Gurion University of the Negev, Department of Health Systems Management- School of Public Health- Guilford Glazer Faculty of Business and Management, Beer Sheva, Israel;(8)Faculty of Health Sciences- Ben-Gurion University of the Negev, Gastroenterology & Hepatology, Metar, Israel;(9)Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- Faculty of Health Sciences- and The National Institute of Biotechnology in the Negev, Beer Sheva, Israel;(10)Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- Faculty of Health Sciences- and The National Institute of Biotechnology in the Negev- Zlotowski Neuroscience Center- and Regenerative Medicine and Stem Cell Research Center, Beer Sheva, Israel

Background

Crohn's disease (CD) is associated with psychological stress and alteration of gut microbiota as compared to healthy individuals. Previous work has reported imbalances in CD patients across four major bacterial phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. We aimed to determine the effect on gut microbiota of a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX), a psychological intervention shown to improve the wellbeing and inflammatory state of CD patients.

Methods

Microbial analysis of stool samples, circulating inflammatory markers and a wide range of psychological parameters related to stress, well-being and daily activities were measured and compared among 25 CD patients before (T1) and after (T2) COBMINDEX, and 25 matched CD wait-list controls at the corresponding time-points T1 and T2. Stool DNA extracts were subjected to 16S amplicon sequencing (Illumina) and analysed for taxonomical abundance, alpha and beta diversity using the QIIME2 pipeline and correlated with inflammatory and clinical parameters. 

Results

Microbial alpha diversity among all CD patients at T1 significantly correlated to the 3 key cytokines: IL-10 (p=0.04, correlation=0.48) , INFg (p=0.02, correlation=0.53), and INFa (p=0.02, correlation=0.51). At T2, while beta diversity was significantly increased in the COBMINDEX group (p=0.03), it was significantly decreased (p=0.0001) among the wait-list controls (Figure 1). Furthermore, compared with the wait-list controls, changes in inflammatory and clinical markers such as INFg, TNFa, IL-6, calprotectin and CRP, occurring following COBMINDEX, were accompanied by changes in the 4 main phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria (Figure 2). Lastly, changes in a variety of unique taxa, not previously implicated in CD, were also associated with changes in inflammatory and clinical markers such as INFg, TNFa, IL-6, calprotectin and CRP in the COBMINDEX but not in wait-list controls (Figure 2).

Conclusion

Our results show that microbial diversity is connected to the inflammatory profile of CD patients, and is significantly altered by COBMINDEX. Moreover, changes in the 4 main phyla that are known to be different among CD patients are linked to changes in various inflammatory markers, demonstrating the microbial-inflammatory relationship among CD patients. Lastly, we found that changes in the abundancies of 7 taxa, hitherto untied to CD in the literature, correlate with inflammatory markers, hinting at new microbial targets in CD.

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