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PP044-MON POSTPRANDIAL PLASMA GLYCINE-CONJUGATED DEOXYCHOLIC ACID LEVELS CORRESPOND WITH PLASMA INSULIN LEVELS IN HEALTHY SUBJECTS
Hormones, mediators and immunity
S139
Conclusion: In UR, the inflammatory markers, such as IL-18, are present in an early stage after birth, probably contributing for the development of renal injury in this model. The lower expression of these markers seems to be directly related to improvement of renal function. Our results suggest that these inflammatory markers can be attenuated by L-arginine. Disclosure of Interest: None Declared
PP043-MON EFFECT OF BIFIDUS BB536 AND ACTIVE HEXOSE CORRELATED COMPOUND ON IMMUNE FUNCTION IN HEALTHY INDIVIDUALS 1
2
3
1
A.H. Chowdhury , M. Camara , A. Kulkarni , D.N. Lobo . 1 Division of Gastrointestinal Surgery, NIHR Nottingham Digestive Diseases Centre Biomedical Research Unit, 2 School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom; 3 Department of Surgery, University of Texas Medical School, Texas, United States Rationale: The probiotic Bifidus BB536, which contains Bifidobacterium longum, and has been shown to have enhanced probiotic effect when given together with the prebiotic, active hexose correlated compound (AHCC). It is proposed that Bifidus 536 and AHCC may improve gastrointestinal (GI) symptoms associated with antibiotic usage and modulate T cell and dendritic cell (DC) phenotypes to favour antiinflammatory responses. Methods: Forty healthy male volunteers, divided into 4 equal groups were randomised to receive either placebo, Bifidus BB536, AHCC or a combination for 13 days in a doubleblind manner. After 7 days volunteers also received 250 mg azithromycin for 5 days. Stool frequency and consistency was assessed throughout the treatment period. T cell Foxp3 expression and peripheral blood DC subsets were assessed prior to treatment and subsequently at 7 and 14 days. Results: Following the ingestion of azithromycin, volunteers taking placebo had an increase in mean±SEM daily stool frequency (1.4±0.3 vs 2.4±0.3; p = 0.042) and stool looseness (2.1±0.4 vs 3.9±0.4; p = 0.004). These symptoms were not increased in volunteers taking Bifidus BB536 or combination treatments with AHCC. Foxp3 expression (0.45±0.1 vs 1.3±0.4; p = 0.002) and IFN-g/IL-4 (p = 0.031) ratios were increased post-treatment in volunteers receiving Bifidus BB536, although differences between groups were not significant. For volunteers receiving combination Bifidus BB536 and AHCC, there was an increase in myeloid compared to plasmacytoid DC counts (61% vs 80%; p = 0.006) at post treatment time points. The mDC2 phenotype was also much more prevalent following combination treatment (0.05% vs 0.16%; p = 0.002). Conclusion: Oral intake of AHCC and Bifidus BB536 may decrease GI symptoms associated with antibiotic usage and modulate immune cell phenotype to favour anti-inflammatory responses. Disclosure of Interest: A. Chowdhury Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan, M. Camara: None Declared, A. Kulkarni: None Declared, D. Lobo Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan
PP044-MON POSTPRANDIAL PLASMA GLYCINE-CONJUGATED DEOXYCHOLIC ACID LEVELS CORRESPOND WITH PLASMA INSULIN LEVELS IN HEALTHY SUBJECTS S. Van Nierop1 , R. Achterbergh2 , L. Lammers3 , H. Eggink1 , F. Vaz4 , R. Mathot3 , J. Romijn2 , M. Soeters1 . 1 Dept. of Endocrinology and Metabolism, 2 Dept. of Internal Medicine, 3 Dept. of Hospital Pharmacy, 4 Laboratory Genetic Metabolic Diseases, AMC, University of Amsterdam, Amsterdam, Netherlands Rationale: Bile acids are important in metabolic signalling through their receptors TGR5 and FXR. We investigated postprandial BA levels in relation to insulin levels in different nutritional conditions. Methods: 7 Volunteers underwent a mixed meal test after a 36 hour fast (F), 3 days of hypercaloric feeding (H) or after an overnight fast (control, C). Hypercaloric feeding consisted of 0.5 L of cream per day, containing 1680 kcal (fat 88%) added to the habitual diet. All subjects underwent all interventions. Serum BA, insulin and glucose levels were measured at 0, 30, 60, 90, 120, 180 and 240 minutes. Individual BAs were measured with HPLC MS. Results: Postprandial glucose excursions were not significantly different between interventions. Insulin AUC was higher after fasting (C 28±10 pmol/L vs F 51±19 pmol/L; p = 0.04). Total BA as well as individual BA species levels in plasma showed a postprandial rise with postprandial peaks of glycineconjugated chenodeoxycholic acid (gCDCA) and deoxycholic acid (gDCA) but there were no differences between the interventions. Insulin levels at 0 and 30 minutes after a meal did not correlate to BA levels. However, in groups C and H, there were positive correlations between insulin at 60 and gDCA levels at 60 minutes (C r = 0.89, p < 0.01; H r = 0.99, p < 0.01), 90 minutes (C r = 0.89, p < 0.01; H r = =0.82, p < 0.05), and 120 minutes (C r = 0.82, p < 0.05; H r = 0.82, p < 0.05). In contrast, fasting abrogated the correlations between insulin and gDCA levels. Conclusion: There was a strong positive correlation between gDCA levels and insulin levels one hour after a meal. This correlation was not detectable for other BA species, which might suggest that gDCA, a strong TGR5 ligand, specifically modulates the postprandial insulin response. Peak postprandial gDCA levels in this study were well above the EC50 for TGR5, supporting a TGR5-mediated effect on insulin secretion. Disclosure of Interest: None Declared
PP045-MON PARENTERAL NUTRITION DECREASES GUT INTERLEUKIN-15 AND 21 LEVELS IN MICE: A POSSIBLE MECHANISM FOR IMPAIRED GUT IMMUNITY DURING LACK OF ENTERAL NUTRITION S. Murakoshi1 , K. Fukatsu2 , T. Moriya3 , M. Yanagawa2 , S. Amenomori2 , H. Yasuhara2 . 1 Surgical Center, Supply Center, 2 Surgical Center, The University of Tokyo Hospital, Bunkyou-ku, 3 Department of Surgery, National Defense Medical College, Tokorozawa, Japan Rationale: Lack of enteral nutrition causes impairment of gut immunity. Changes in gut cytokine milieu have been pro-
S139
Conclusion: In UR, the inflammatory markers, such as IL-18, are present in an early stage after birth, probably contributing for the development of renal injury in this model. The lower expression of these markers seems to be directly related to improvement of renal function. Our results suggest that these inflammatory markers can be attenuated by L-arginine. Disclosure of Interest: None Declared
PP043-MON EFFECT OF BIFIDUS BB536 AND ACTIVE HEXOSE CORRELATED COMPOUND ON IMMUNE FUNCTION IN HEALTHY INDIVIDUALS 1
2
3
1
A.H. Chowdhury , M. Camara , A. Kulkarni , D.N. Lobo . 1 Division of Gastrointestinal Surgery, NIHR Nottingham Digestive Diseases Centre Biomedical Research Unit, 2 School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom; 3 Department of Surgery, University of Texas Medical School, Texas, United States Rationale: The probiotic Bifidus BB536, which contains Bifidobacterium longum, and has been shown to have enhanced probiotic effect when given together with the prebiotic, active hexose correlated compound (AHCC). It is proposed that Bifidus 536 and AHCC may improve gastrointestinal (GI) symptoms associated with antibiotic usage and modulate T cell and dendritic cell (DC) phenotypes to favour antiinflammatory responses. Methods: Forty healthy male volunteers, divided into 4 equal groups were randomised to receive either placebo, Bifidus BB536, AHCC or a combination for 13 days in a doubleblind manner. After 7 days volunteers also received 250 mg azithromycin for 5 days. Stool frequency and consistency was assessed throughout the treatment period. T cell Foxp3 expression and peripheral blood DC subsets were assessed prior to treatment and subsequently at 7 and 14 days. Results: Following the ingestion of azithromycin, volunteers taking placebo had an increase in mean±SEM daily stool frequency (1.4±0.3 vs 2.4±0.3; p = 0.042) and stool looseness (2.1±0.4 vs 3.9±0.4; p = 0.004). These symptoms were not increased in volunteers taking Bifidus BB536 or combination treatments with AHCC. Foxp3 expression (0.45±0.1 vs 1.3±0.4; p = 0.002) and IFN-g/IL-4 (p = 0.031) ratios were increased post-treatment in volunteers receiving Bifidus BB536, although differences between groups were not significant. For volunteers receiving combination Bifidus BB536 and AHCC, there was an increase in myeloid compared to plasmacytoid DC counts (61% vs 80%; p = 0.006) at post treatment time points. The mDC2 phenotype was also much more prevalent following combination treatment (0.05% vs 0.16%; p = 0.002). Conclusion: Oral intake of AHCC and Bifidus BB536 may decrease GI symptoms associated with antibiotic usage and modulate immune cell phenotype to favour anti-inflammatory responses. Disclosure of Interest: A. Chowdhury Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan, M. Camara: None Declared, A. Kulkarni: None Declared, D. Lobo Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan
PP044-MON POSTPRANDIAL PLASMA GLYCINE-CONJUGATED DEOXYCHOLIC ACID LEVELS CORRESPOND WITH PLASMA INSULIN LEVELS IN HEALTHY SUBJECTS S. Van Nierop1 , R. Achterbergh2 , L. Lammers3 , H. Eggink1 , F. Vaz4 , R. Mathot3 , J. Romijn2 , M. Soeters1 . 1 Dept. of Endocrinology and Metabolism, 2 Dept. of Internal Medicine, 3 Dept. of Hospital Pharmacy, 4 Laboratory Genetic Metabolic Diseases, AMC, University of Amsterdam, Amsterdam, Netherlands Rationale: Bile acids are important in metabolic signalling through their receptors TGR5 and FXR. We investigated postprandial BA levels in relation to insulin levels in different nutritional conditions. Methods: 7 Volunteers underwent a mixed meal test after a 36 hour fast (F), 3 days of hypercaloric feeding (H) or after an overnight fast (control, C). Hypercaloric feeding consisted of 0.5 L of cream per day, containing 1680 kcal (fat 88%) added to the habitual diet. All subjects underwent all interventions. Serum BA, insulin and glucose levels were measured at 0, 30, 60, 90, 120, 180 and 240 minutes. Individual BAs were measured with HPLC MS. Results: Postprandial glucose excursions were not significantly different between interventions. Insulin AUC was higher after fasting (C 28±10 pmol/L vs F 51±19 pmol/L; p = 0.04). Total BA as well as individual BA species levels in plasma showed a postprandial rise with postprandial peaks of glycineconjugated chenodeoxycholic acid (gCDCA) and deoxycholic acid (gDCA) but there were no differences between the interventions. Insulin levels at 0 and 30 minutes after a meal did not correlate to BA levels. However, in groups C and H, there were positive correlations between insulin at 60 and gDCA levels at 60 minutes (C r = 0.89, p < 0.01; H r = 0.99, p < 0.01), 90 minutes (C r = 0.89, p < 0.01; H r = =0.82, p < 0.05), and 120 minutes (C r = 0.82, p < 0.05; H r = 0.82, p < 0.05). In contrast, fasting abrogated the correlations between insulin and gDCA levels. Conclusion: There was a strong positive correlation between gDCA levels and insulin levels one hour after a meal. This correlation was not detectable for other BA species, which might suggest that gDCA, a strong TGR5 ligand, specifically modulates the postprandial insulin response. Peak postprandial gDCA levels in this study were well above the EC50 for TGR5, supporting a TGR5-mediated effect on insulin secretion. Disclosure of Interest: None Declared
PP045-MON PARENTERAL NUTRITION DECREASES GUT INTERLEUKIN-15 AND 21 LEVELS IN MICE: A POSSIBLE MECHANISM FOR IMPAIRED GUT IMMUNITY DURING LACK OF ENTERAL NUTRITION S. Murakoshi1 , K. Fukatsu2 , T. Moriya3 , M. Yanagawa2 , S. Amenomori2 , H. Yasuhara2 . 1 Surgical Center, Supply Center, 2 Surgical Center, The University of Tokyo Hospital, Bunkyou-ku, 3 Department of Surgery, National Defense Medical College, Tokorozawa, Japan Rationale: Lack of enteral nutrition causes impairment of gut immunity. Changes in gut cytokine milieu have been pro-