- Email: [email protected]
Sa1983 Differential Reprogramming of Resting Metabolic Energy After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Mice
predict response to lactulose or synthetic sugar challenge as part of IP tests. Further, lactulose is metabolized by colonic bacteria to produce short-chain fatty acids, such as butyric acid, which are known to modulate the epithelial barriers in cell and animal models. Because alterations in IP and epithelial barriers are thought to contribute to various pathologies, including those stemming from chronic inflammation, our data provide insights for studies aiming to understand the contribution of microbes and their metabolic products to the epithelium.
Proportion of patients with fecal calprotectin £ 100 mg/kg and CRP£5 mg/L across different infliximab trough concentrations
Sa1981 Predictors of Loss of Response to Adalimumab Therapy; the Importance of Therapeutic Drug Monitoring in Inflammatory Bowel Diseases Zsuzsanna Kurti, Zsuzsanna Vegh, Petra A. Golovics, Krisztina Gecse, Lorant Gonczi, Mariann Rutka, Klaudia Farkas, Tamas Molnar, Peter L. Lakatos
Figure 1. Correlation of IVP to lactulose in urine.
Background and aim Therapeutic drug monitoring (TDM) measuring drug trough levels (TL) and antidrug antibodies (ADA) may aid the therapeutic decision in patients with inflammatory bowel disease (IBD) who loose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response to adalimumab therapy and the role of the therapeutic drug monitoring to predict the loss of response in adalimumab treated IBD patients. Methods 74 IBD patients (with 94 TDM measurements, CD/UC 59/ 15, male/female 32/42, mean age CD/UC: 38/31 years, mean duration of adalimumab therapy CD/UC: 147.6/43.7 weeks) were enrolled in this consecutive cohort from two referral IBD centres in Hungary. Demographic data were comprehensively collected and a harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity at the time of the TL and ADA measurement were recorded. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were done by commercial ELISA (LISA TRACKER, Theradiag, France). Results Among 74 IBD patients, the probability of ADA positivity and low TL (<4.5 µg/mL) was 8.1% and 13.8% in the first year and 11.4% and 28.8% and in the second year after start of adalimumab therapy in Kaplan-Meier analysis. The frequency of previous and current steroid and azathioprine exposure were 95.9%/29.7% and 73.3%/53.3% and previous anti-TNF therapy was present in 74% (in CD 69%, in UC 93.3%) in the IBD cohort. Dose intensification was needed in 38.7% during the study period. The combination of normal TL and no ADA, normal TL and high ADA, low TL and no ADA and low TL and high ADA were observed in 63.5%, 6.8%, 23% and 6.8% at TDM measurement. Predictors of the dose intensification were female gender (p=0.06, HR: 2.1), concomitant steroid therapy (p=0.01, HR: 2.57) and ADA positivity (p=0.005, HR: 3.26) with Cox-regression model (p<0.05). Predictors of loss of response were female gender (p=0.004, HR: 4.9), dose intensification (p=0.009, HR: 3.75) and there was a positive trend for concomitant steroid therapy (p=0.06, HR: 2.71) and previous anti-TNF therapy (p=0.15, HR: 2.39). Predictors remained unchanged if the 94 TDM episodes were analysed separately. Conclusions Our results suggest that ADA development, low TL and need for dose intensification are frequent during adalimumab therapy and support the use of routine TDM assessment in IBD patients. Female gender, concomitant steroid therapy and ADA positivity were predictors of dose intensification and female gender and dose intensification predicted loss of response.
Figure 2.The abundance of each bacterial family represented among the 65 correlations. Blue indicates a positive correlation with the VP/lactulose ratio while orange indicates a negative correlations. Members of the Lactobacillaceae were mostly negatively correlated to ratio deviation.
Sa1983 Differential Reprogramming of Resting Metabolic Energy After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Mice Mohamad Mokadem, Nicholas W. Garcia, Ruth A. Riedl, Colin M. Burnett, Justin L. Grobe Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most common bariatric procedures performed for weight reduction. Traditionally, bariatric procedures were divided into "restrictive", ‘malabsorptive" or "mixed" categories based on the rearranged surgical anatomy. However, despite having very different anatomical re-arrangement, these 2 bariatric surgeries seem to share several physiologic changes that are closely associated with regulation of energy, glucose and lipid metabolism such as the changes in gut-secreted hormones, for example. Therefore, RYGB and SG are currently labeled by many as "Metabolic" surgeries. Yet, the difference in energy balance regulation between the two procedures is not very well known and the exact mechanism by which each surgery exerts its weight regulatory effects is still not completely understood. Methods: We wanted to measure, using direct and indirect calorimetry (or respirometer), the resting metabolic rate (RMR) in diet-induced obese (DIO) mice after RYGB and SG. We also wanted to assess for any difference in aerobic vs non-aerobic elements of RMR between the two surgeries. Results: We found that feeding efficiency (defined as body weight gain per energy unit consumed) is decreased while food intake is rather unchanged after RYGB in DIO mice (Figure 1A-C). On the other hand, we found that food intake is rather decreased after SG, at least during the first 4 weeks, but feeding efficiency is relatively unchanged (Figure 1D-E). After correcting for weight and body-composition, we showed that DIO mice who underwent RYGB but not SG displayed an increase in total RMR compared to sham-operated counterparts (Figure 2A). We also found that the aerobic component of the RMR did not significantly change after RYGB while the anaerobic component increased significantly when compared to shamoperated counterparts with a difference close to 200% (Figure 2B). There is growing evidence in the literature about the role of gut microbiome in the development of obesity as well as in the effects of bariatric surgery itself. We wanted to examine the effects of transferring gut microbiome from RYGB vs sham-operated mice into DIO mice recipients on energy balance.
Sa1982 Liquid Chromatography Mass Spectrometry Based Analysis of Human Response to Synthetic Sugar Challenge and the Microbiome Paule V. Joseph, Nicolaas H. Fourie, Eric Ferguson, Sarah K. Abey, Peter Walter, LeeAnne B. Sherwin, Bridgett Rahim-Williams, Lorenzo Leggio, Wendy A. Henderson Background: Lactulose, a synthetic sugar, is used to assess intestinal permeability (IP) and is known to induce visceral sensitivity or pain. The microbiome mediates IP, VP, and lactulose metabolism in the gut. We aimed to predict VP response to oral lactulose challenge using baseline microbiome and to develop a predictive algorithm for a VP/IP lactulose metabolism. Methods: Eighteen participants were recruited (27.94±4.27 years, BMI 25.62±4.24, 66% female, 50% Caucasian), consented, had baseline microbiome sampling prior to ingestion of a lactulose-containing IP test solution. Urine was collected over 5 hours following ingestion. Patients had no H. pylori, C. difficile, parasitic infections or evidence of organic disease. PhyloChip microbiome analysis, liquid chromatography mass spectrometry urinary metabolism (Thermo Scientific Q-Exactive LC-MS), and self-reported VP (Gastrointestinal Pain Pointer) were measured. Results: Eleven of 18 reported VP. Urinary lactulose excretion positively correlated with VP (R2>0.5, Figure 1), significantly correlated to 65 OTUs (R2>0.25), and 45 were positively correlated (Figure 2). The Lactobacillaceae and Clostridiali, are known to harbor members with disaccharide metabolizing capabilities. The Lactobacillaceae and Clostridiali are disproportionately represented among the group of 65 correlated bacteria compared to the overall richness profile. Discussion: The microbial OTU-specific correlation to participants' VP/IP lactulose ratio provides a trend which can be utilized to
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[min 2.1, max 6.0]) and high trough level (median 10.2 µg/ml [min 6.4, max 12.0]). In each group we calculated median fecal calprotectin and CRP levels and proportion of patients with fecal calprotection below 100 mg/kg and with normal CRP ( £5 mg/L). To test for differences across studied groups we used Mann-Whitney U test and Chi-squared test. Results: Median fecal calprotectin levels and CRP were lower in patients with high infliximab trough levels (fecal calprotectin median 73 mg/kg [IQR: 30-319]; CRP median 3 mg/L [IQR:3-6]) compared to patients with intermediate (fecal calprotectin median 140 mg/kg [IQR: 56-461]; CRP median 3 mg/L [IQR:3-11]) and low infliximab trough levels (fecal calprotectin median 232 mg/kg [IQR: 101-747]; CRP median 9 mg/L [IQR:3-26]) (fecal calprotectin p= 0.046; CRP p= 0.02). Similar was observed for proportion of patients with fecal calprotectin below 100 mg/kg and normal CRP (Table 1). Conclusion: Our data indicate that infliximab trough levels > 6.4 µg/ml are associated with better control of inflammation (lower fecal calprotectin and CRP) in IBD on infliximab maintenance treatment compared to patients with lower infliximab trough levels.
AGA Abstracts
We found that food intake did not differ between DIO mice receiving RYGB vs shamcollected microbiome. Further information regarding total energy expenditure and RMR in DIO mice- after microbial transfer- are still in progress. Conclusion: We showed that at least in rodents, RYGB induces its weight-regulatory effects by increasing energy expenditure; specifically the anaerobic component of the RMR while SG induces its weight-regulatory effects predominantly by decreasing food intake. The role of gut microbiome in energy regulation after bariatric surgery is still unclear.
acetate, butyrate, and valerate amount. However, total SCFA had negative correlation to blood insulin level and homeostasis model of insulin resistance (HOMA-IR) (r=−0.325; R2=0.106; p=0.015, and r=−0.338; R2=0.114; p=0.011, respectively). Propionate showed negative correlation to insulin and HOMA-IR (r=−0.310; R2=0.096; p=0.020, and r=−0.335; R2=0.112; p=0.012, respectively). Acetate had negative correlation to insulin and HOMAIR (r=−0.324; R2=0.105; p=0.015, and r=−0.324; R2=0.105; p=0.015, respectively). Valerate was negative correlation to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (r=−0.262; R2=0.069; p=0.049, and r=−0.307; R2=0.095; p=0.020, respectively). Butyrate was positive correlation to high-density lipoprotein (HDL) cholesterol and highmolecular-weight adiponectin (r=0.360; R2=0.130; p=0.006, and r=0.302; R2=0.091; p= 0.028, respectively). Conclusion: Gut environments including microbiome and SCFA have effects on metabolism of type 2 diabetes patients. A better understanding of this relationship might lead to better therapies and prophylaxis for type 2 diabetes.
Sa1985 Microbiota-Related Acute Phase Proteins Are Predictors of Cardiometabolic Complications in Survivors of Pediatric Leukemia Valerie Marcil, Sophia Morel, Jade England, Catherine Bazinet, Mariia Samoilenko, Genevieve Lefebvre, Maja Krajinovic, Caroline Laverdiere, Daniel Sinnett, Emile Levy BACKGROUND and AIMS: It is estimated that about 70% of survivors of childhood acute lymphoblastic leukemia (cALL) have substantial long-term morbidities as a result of their treatments. In particular, growing evidence indicates the high occurrence of obesity, glucose intolerance, dyslipidemia and hypertension. However, the exact factors leading to these complications remain unknown. Absorption from the gut of bacterial lipopolysaccharides (LPS) and its binding to LPS-binding protein (LBP) in circulation may initiate an inflammatory response and contribute to the development of cardiometabolic diseases. Besides, several studies support a direct interaction between microbiota composition and plasma levels of LPS, LBP and C reactive protein (CRP). Since chemotherapy treatments during childhood could contribute to elicit changes in gut microbiota composition, we evaluated the predictive value of circulating LPS, LBP and high-sensitivity (hs) CRP in cardiometabolic complications of cALL survivors. METHODS: Patients (n=190, mean age of 22.8) were recruited as part of the PETALE project at Sainte-Justine Hospital, Montreal, Canada. Extensive clinical and biochemical data were collected and compared to cut-off values for age and gender. LPS, LBP and CRP were measured using ELISA kits and a log-binomial regression model adjusted for age, gender and cranial radiotherapy exposure was used to estimate relative risk (RR) and 95% confidence intervals (CI). RESULTS: Results demonstrate a high prevalence of obesity (65%), insulin resistance (19%) and dyslipidemia (45%), while pre-hypertension was mostly prevalent in young men (20%). We also found that 44% of the cohort accumulated at least 2 risk factors. Mean levels (±SEM) of LPS, LBP and hs-CRP were respectively 12.9 ± 0.4 ng/mL, 28.3 ± 0.8 µg/ml and 3.1 ± 0.3 mg/L. Regression analysis revealed that LBP levels within the third tertile was associated with higher risk of obesity (RR: 2.18, CI: 1.323.60), dyslipidemia (RR: 1.92, CI: 1.23-3.00), insulin resistance (RR: 3.78, CI: 1.54-9.28), low HDL-cholesterol (RR: 3.44, CI: 1.56-7.57) and with having 2 or more complications (RR: 2.30, CI: 1.43-3.73). Furthermore, subjects with abnormal hs-CRP levels (>5 mg/L) had higher risk of obesity (RR: 1.86, CI: 1.51-2.32), insulin resistance (RR: 2.79, CI: 1.445.01) and combination of at least 2 risk factors (RR: 1.87, CI: 1.36-2.57). LPS levels were not significantly predictive of patients' cardiometabolic risk. CONCLUSIONS: These results indicate that the microbiota-related inflammatory proteins LBP and CRP are highly predictive of cardiometabolic complications in survivors of pediatric leukemia. It is conceivable that the intensive treatments administrated to cALL patients alter gut microbiota composition and contribute the development of cardiometabolic complications in this population.
RYGB and SG induce weight reduction via different mechanims. Body weight curves expressed as a percentage of pre-operative body weight for bariatric and sham-operated DIO mice over a period of 4-5 weeks (A and D). Average daily food inatke expressed as g of high-fat diet per day for bariatric and sham-operated DIO mice during post operative week 2 and 3 (B and E). Feeding efficiency expressed as mg of body weight gain per kilojoule consumed in bariatric and sham-operated DIO mice (C and F). n=5-7 for bariatric-and sham-operated mice.
Sa1986 Impact of Short-Chain Galactooligosaccharides on the Gut Microbiome of Lactose Intolerant Individuals M. Andrea Azcarate-Peril, Andrew Ritter, Dennis Savaiano, Todd Klaenhammer
Differential reprogramming of resting metabolic rate (RMR) after RYGB and SG. Total RMR expressed as Kcal/hour in relation to body mass in RYGB and SG operated DIO mice (A). Average total RMR, aerobic RMR, and anaerobic RMR in RYGB vs sham-operated DIO mice (B). n=4-5 for bariatric and sham-operated mice.
Directed modulation of the colonic bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multi-site placebo controlled trial was conducted in human subjects and demonstrated that administration of a highly purified (> 95%), short chain galacto-oligosaccharide (GOS), designated RP-G28, significantly improved clinical outcomes for lactose digestion and tolerance. In these individuals, stool samples were collected pre-treatment (Day 0), after GOS treatment (Day 36), and finally 30 days after GOS feeding stopped and consumption of dairy products was encouraged (Day 66). In this study, changes in the fecal microbiome were investigated using 16S rRNA amplicon pyrosequencing and highthroughput quantitative PCR. At 36 days, bifidobacterial populations were increased in 27 of 30 of GOS subjects (90%) demonstrating a bifidogenic response, in vivo. Principal coordinate analyses further showed a statistically significant shift in the microbiome in subjects fed GOS. Relative abundance of lactose fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus, were significantly increased in response to GOS. When dairy was introduced into the diet, lactose-fermenting Roseburia species increased from 36 to 66 days. The results indicated a definitive change in the fecal microbiome of lactose intolerant individuals, increasing lactose-metabolizing bacteria that were responsive to dietary adaptation to GOS and correlated with clinical outcomes toward lactose tolerance.
Sa1984 Influence of Intestinal Microbiome and Short Chain Fatty Acid on Metabolism in Type 2 Diabetes Patients Makoto Sasaki, Tomoya Sugiyama, Seiji Noguchi, Hiroki Kitahora, Akihiro Shimozato, Yoshiharu Yamaguchi, Kazunori Adachi, Noriko Okaniwa, Shigeki Goji, Atsushi Tanabe, Hisatsugu Noda, Yoshihiro Kondo, Yoshitsugi Ito, Shinya Izawa, Masahide Ebi, Naotaka Ogasawara, Yasushi Funaki, Kunio Kasugai Background & Aim: Evidence is accumulating that the intestinal microbiota, in addition to other major factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. We have reported gut dysbiosis in type 2 diabetes patients (BMC Gastroenterol. 2013;13:81). In this study, we examined relationship among gut microbiota, blood metabolism markers, dietary habits, and fecal short chain fatty acid in type 2 diabetes patients. Methods: Sixty type 2 diabetes patients (25 female and 35 men, mean age; 62.7 years old) were recruited in this study. Blood, fecal samples, and databased short food frequency questionnaires were analyzed. Results: Total energy intake was 1693 (948 - 2781) Kcal/day. Protein, fat, carbohydrate, and fiber intake were 55.0 (21.6 - 88.1) g, 42.3 (23.8 - 70.3) g, 244.7 (107.7 - 450.7) g, and 11.8 (6.4 - 21.2) g, respectively. Dietary habits (high protein, high fat, and high carbohydrate) were associated with increase of gut bacteria (Clostridium cluster XI, Clostridium cluster XI, and Clostridium cluster IV, respectively) (r= 0.363; R2=0.131; p=0.005, r=0.301; R2=0.091; p=0.021, and r=0.266; R2=0.071; p=0.042, respectively), and associated with decrease of gut bacteria ( Lactobacillales,Clostridium cluster IV, and Bifidobacterium, respectively) (r=−0.275; R2=0.076; p=0.035, r=−0.261; R2=0.068; p=0.046, and r=−0.420; R2=0.176; p=0.001, respectively). Dietary fiber, protein, fat, and carbohydrate amount had no influence to intestinal short chain fatty acid (SCFA), propionate,
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Proportion of patients with fecal calprotectin £ 100 mg/kg and CRP£5 mg/L across different infliximab trough concentrations
Sa1981 Predictors of Loss of Response to Adalimumab Therapy; the Importance of Therapeutic Drug Monitoring in Inflammatory Bowel Diseases Zsuzsanna Kurti, Zsuzsanna Vegh, Petra A. Golovics, Krisztina Gecse, Lorant Gonczi, Mariann Rutka, Klaudia Farkas, Tamas Molnar, Peter L. Lakatos
Figure 1. Correlation of IVP to lactulose in urine.
Background and aim Therapeutic drug monitoring (TDM) measuring drug trough levels (TL) and antidrug antibodies (ADA) may aid the therapeutic decision in patients with inflammatory bowel disease (IBD) who loose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response to adalimumab therapy and the role of the therapeutic drug monitoring to predict the loss of response in adalimumab treated IBD patients. Methods 74 IBD patients (with 94 TDM measurements, CD/UC 59/ 15, male/female 32/42, mean age CD/UC: 38/31 years, mean duration of adalimumab therapy CD/UC: 147.6/43.7 weeks) were enrolled in this consecutive cohort from two referral IBD centres in Hungary. Demographic data were comprehensively collected and a harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity at the time of the TL and ADA measurement were recorded. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were done by commercial ELISA (LISA TRACKER, Theradiag, France). Results Among 74 IBD patients, the probability of ADA positivity and low TL (<4.5 µg/mL) was 8.1% and 13.8% in the first year and 11.4% and 28.8% and in the second year after start of adalimumab therapy in Kaplan-Meier analysis. The frequency of previous and current steroid and azathioprine exposure were 95.9%/29.7% and 73.3%/53.3% and previous anti-TNF therapy was present in 74% (in CD 69%, in UC 93.3%) in the IBD cohort. Dose intensification was needed in 38.7% during the study period. The combination of normal TL and no ADA, normal TL and high ADA, low TL and no ADA and low TL and high ADA were observed in 63.5%, 6.8%, 23% and 6.8% at TDM measurement. Predictors of the dose intensification were female gender (p=0.06, HR: 2.1), concomitant steroid therapy (p=0.01, HR: 2.57) and ADA positivity (p=0.005, HR: 3.26) with Cox-regression model (p<0.05). Predictors of loss of response were female gender (p=0.004, HR: 4.9), dose intensification (p=0.009, HR: 3.75) and there was a positive trend for concomitant steroid therapy (p=0.06, HR: 2.71) and previous anti-TNF therapy (p=0.15, HR: 2.39). Predictors remained unchanged if the 94 TDM episodes were analysed separately. Conclusions Our results suggest that ADA development, low TL and need for dose intensification are frequent during adalimumab therapy and support the use of routine TDM assessment in IBD patients. Female gender, concomitant steroid therapy and ADA positivity were predictors of dose intensification and female gender and dose intensification predicted loss of response.
Figure 2.The abundance of each bacterial family represented among the 65 correlations. Blue indicates a positive correlation with the VP/lactulose ratio while orange indicates a negative correlations. Members of the Lactobacillaceae were mostly negatively correlated to ratio deviation.
Sa1983 Differential Reprogramming of Resting Metabolic Energy After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Mice Mohamad Mokadem, Nicholas W. Garcia, Ruth A. Riedl, Colin M. Burnett, Justin L. Grobe Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most common bariatric procedures performed for weight reduction. Traditionally, bariatric procedures were divided into "restrictive", ‘malabsorptive" or "mixed" categories based on the rearranged surgical anatomy. However, despite having very different anatomical re-arrangement, these 2 bariatric surgeries seem to share several physiologic changes that are closely associated with regulation of energy, glucose and lipid metabolism such as the changes in gut-secreted hormones, for example. Therefore, RYGB and SG are currently labeled by many as "Metabolic" surgeries. Yet, the difference in energy balance regulation between the two procedures is not very well known and the exact mechanism by which each surgery exerts its weight regulatory effects is still not completely understood. Methods: We wanted to measure, using direct and indirect calorimetry (or respirometer), the resting metabolic rate (RMR) in diet-induced obese (DIO) mice after RYGB and SG. We also wanted to assess for any difference in aerobic vs non-aerobic elements of RMR between the two surgeries. Results: We found that feeding efficiency (defined as body weight gain per energy unit consumed) is decreased while food intake is rather unchanged after RYGB in DIO mice (Figure 1A-C). On the other hand, we found that food intake is rather decreased after SG, at least during the first 4 weeks, but feeding efficiency is relatively unchanged (Figure 1D-E). After correcting for weight and body-composition, we showed that DIO mice who underwent RYGB but not SG displayed an increase in total RMR compared to sham-operated counterparts (Figure 2A). We also found that the aerobic component of the RMR did not significantly change after RYGB while the anaerobic component increased significantly when compared to shamoperated counterparts with a difference close to 200% (Figure 2B). There is growing evidence in the literature about the role of gut microbiome in the development of obesity as well as in the effects of bariatric surgery itself. We wanted to examine the effects of transferring gut microbiome from RYGB vs sham-operated mice into DIO mice recipients on energy balance.
Sa1982 Liquid Chromatography Mass Spectrometry Based Analysis of Human Response to Synthetic Sugar Challenge and the Microbiome Paule V. Joseph, Nicolaas H. Fourie, Eric Ferguson, Sarah K. Abey, Peter Walter, LeeAnne B. Sherwin, Bridgett Rahim-Williams, Lorenzo Leggio, Wendy A. Henderson Background: Lactulose, a synthetic sugar, is used to assess intestinal permeability (IP) and is known to induce visceral sensitivity or pain. The microbiome mediates IP, VP, and lactulose metabolism in the gut. We aimed to predict VP response to oral lactulose challenge using baseline microbiome and to develop a predictive algorithm for a VP/IP lactulose metabolism. Methods: Eighteen participants were recruited (27.94±4.27 years, BMI 25.62±4.24, 66% female, 50% Caucasian), consented, had baseline microbiome sampling prior to ingestion of a lactulose-containing IP test solution. Urine was collected over 5 hours following ingestion. Patients had no H. pylori, C. difficile, parasitic infections or evidence of organic disease. PhyloChip microbiome analysis, liquid chromatography mass spectrometry urinary metabolism (Thermo Scientific Q-Exactive LC-MS), and self-reported VP (Gastrointestinal Pain Pointer) were measured. Results: Eleven of 18 reported VP. Urinary lactulose excretion positively correlated with VP (R2>0.5, Figure 1), significantly correlated to 65 OTUs (R2>0.25), and 45 were positively correlated (Figure 2). The Lactobacillaceae and Clostridiali, are known to harbor members with disaccharide metabolizing capabilities. The Lactobacillaceae and Clostridiali are disproportionately represented among the group of 65 correlated bacteria compared to the overall richness profile. Discussion: The microbial OTU-specific correlation to participants' VP/IP lactulose ratio provides a trend which can be utilized to
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[min 2.1, max 6.0]) and high trough level (median 10.2 µg/ml [min 6.4, max 12.0]). In each group we calculated median fecal calprotectin and CRP levels and proportion of patients with fecal calprotection below 100 mg/kg and with normal CRP ( £5 mg/L). To test for differences across studied groups we used Mann-Whitney U test and Chi-squared test. Results: Median fecal calprotectin levels and CRP were lower in patients with high infliximab trough levels (fecal calprotectin median 73 mg/kg [IQR: 30-319]; CRP median 3 mg/L [IQR:3-6]) compared to patients with intermediate (fecal calprotectin median 140 mg/kg [IQR: 56-461]; CRP median 3 mg/L [IQR:3-11]) and low infliximab trough levels (fecal calprotectin median 232 mg/kg [IQR: 101-747]; CRP median 9 mg/L [IQR:3-26]) (fecal calprotectin p= 0.046; CRP p= 0.02). Similar was observed for proportion of patients with fecal calprotectin below 100 mg/kg and normal CRP (Table 1). Conclusion: Our data indicate that infliximab trough levels > 6.4 µg/ml are associated with better control of inflammation (lower fecal calprotectin and CRP) in IBD on infliximab maintenance treatment compared to patients with lower infliximab trough levels.
AGA Abstracts
We found that food intake did not differ between DIO mice receiving RYGB vs shamcollected microbiome. Further information regarding total energy expenditure and RMR in DIO mice- after microbial transfer- are still in progress. Conclusion: We showed that at least in rodents, RYGB induces its weight-regulatory effects by increasing energy expenditure; specifically the anaerobic component of the RMR while SG induces its weight-regulatory effects predominantly by decreasing food intake. The role of gut microbiome in energy regulation after bariatric surgery is still unclear.
acetate, butyrate, and valerate amount. However, total SCFA had negative correlation to blood insulin level and homeostasis model of insulin resistance (HOMA-IR) (r=−0.325; R2=0.106; p=0.015, and r=−0.338; R2=0.114; p=0.011, respectively). Propionate showed negative correlation to insulin and HOMA-IR (r=−0.310; R2=0.096; p=0.020, and r=−0.335; R2=0.112; p=0.012, respectively). Acetate had negative correlation to insulin and HOMAIR (r=−0.324; R2=0.105; p=0.015, and r=−0.324; R2=0.105; p=0.015, respectively). Valerate was negative correlation to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (r=−0.262; R2=0.069; p=0.049, and r=−0.307; R2=0.095; p=0.020, respectively). Butyrate was positive correlation to high-density lipoprotein (HDL) cholesterol and highmolecular-weight adiponectin (r=0.360; R2=0.130; p=0.006, and r=0.302; R2=0.091; p= 0.028, respectively). Conclusion: Gut environments including microbiome and SCFA have effects on metabolism of type 2 diabetes patients. A better understanding of this relationship might lead to better therapies and prophylaxis for type 2 diabetes.
Sa1985 Microbiota-Related Acute Phase Proteins Are Predictors of Cardiometabolic Complications in Survivors of Pediatric Leukemia Valerie Marcil, Sophia Morel, Jade England, Catherine Bazinet, Mariia Samoilenko, Genevieve Lefebvre, Maja Krajinovic, Caroline Laverdiere, Daniel Sinnett, Emile Levy BACKGROUND and AIMS: It is estimated that about 70% of survivors of childhood acute lymphoblastic leukemia (cALL) have substantial long-term morbidities as a result of their treatments. In particular, growing evidence indicates the high occurrence of obesity, glucose intolerance, dyslipidemia and hypertension. However, the exact factors leading to these complications remain unknown. Absorption from the gut of bacterial lipopolysaccharides (LPS) and its binding to LPS-binding protein (LBP) in circulation may initiate an inflammatory response and contribute to the development of cardiometabolic diseases. Besides, several studies support a direct interaction between microbiota composition and plasma levels of LPS, LBP and C reactive protein (CRP). Since chemotherapy treatments during childhood could contribute to elicit changes in gut microbiota composition, we evaluated the predictive value of circulating LPS, LBP and high-sensitivity (hs) CRP in cardiometabolic complications of cALL survivors. METHODS: Patients (n=190, mean age of 22.8) were recruited as part of the PETALE project at Sainte-Justine Hospital, Montreal, Canada. Extensive clinical and biochemical data were collected and compared to cut-off values for age and gender. LPS, LBP and CRP were measured using ELISA kits and a log-binomial regression model adjusted for age, gender and cranial radiotherapy exposure was used to estimate relative risk (RR) and 95% confidence intervals (CI). RESULTS: Results demonstrate a high prevalence of obesity (65%), insulin resistance (19%) and dyslipidemia (45%), while pre-hypertension was mostly prevalent in young men (20%). We also found that 44% of the cohort accumulated at least 2 risk factors. Mean levels (±SEM) of LPS, LBP and hs-CRP were respectively 12.9 ± 0.4 ng/mL, 28.3 ± 0.8 µg/ml and 3.1 ± 0.3 mg/L. Regression analysis revealed that LBP levels within the third tertile was associated with higher risk of obesity (RR: 2.18, CI: 1.323.60), dyslipidemia (RR: 1.92, CI: 1.23-3.00), insulin resistance (RR: 3.78, CI: 1.54-9.28), low HDL-cholesterol (RR: 3.44, CI: 1.56-7.57) and with having 2 or more complications (RR: 2.30, CI: 1.43-3.73). Furthermore, subjects with abnormal hs-CRP levels (>5 mg/L) had higher risk of obesity (RR: 1.86, CI: 1.51-2.32), insulin resistance (RR: 2.79, CI: 1.445.01) and combination of at least 2 risk factors (RR: 1.87, CI: 1.36-2.57). LPS levels were not significantly predictive of patients' cardiometabolic risk. CONCLUSIONS: These results indicate that the microbiota-related inflammatory proteins LBP and CRP are highly predictive of cardiometabolic complications in survivors of pediatric leukemia. It is conceivable that the intensive treatments administrated to cALL patients alter gut microbiota composition and contribute the development of cardiometabolic complications in this population.
RYGB and SG induce weight reduction via different mechanims. Body weight curves expressed as a percentage of pre-operative body weight for bariatric and sham-operated DIO mice over a period of 4-5 weeks (A and D). Average daily food inatke expressed as g of high-fat diet per day for bariatric and sham-operated DIO mice during post operative week 2 and 3 (B and E). Feeding efficiency expressed as mg of body weight gain per kilojoule consumed in bariatric and sham-operated DIO mice (C and F). n=5-7 for bariatric-and sham-operated mice.
Sa1986 Impact of Short-Chain Galactooligosaccharides on the Gut Microbiome of Lactose Intolerant Individuals M. Andrea Azcarate-Peril, Andrew Ritter, Dennis Savaiano, Todd Klaenhammer
Differential reprogramming of resting metabolic rate (RMR) after RYGB and SG. Total RMR expressed as Kcal/hour in relation to body mass in RYGB and SG operated DIO mice (A). Average total RMR, aerobic RMR, and anaerobic RMR in RYGB vs sham-operated DIO mice (B). n=4-5 for bariatric and sham-operated mice.
Directed modulation of the colonic bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multi-site placebo controlled trial was conducted in human subjects and demonstrated that administration of a highly purified (> 95%), short chain galacto-oligosaccharide (GOS), designated RP-G28, significantly improved clinical outcomes for lactose digestion and tolerance. In these individuals, stool samples were collected pre-treatment (Day 0), after GOS treatment (Day 36), and finally 30 days after GOS feeding stopped and consumption of dairy products was encouraged (Day 66). In this study, changes in the fecal microbiome were investigated using 16S rRNA amplicon pyrosequencing and highthroughput quantitative PCR. At 36 days, bifidobacterial populations were increased in 27 of 30 of GOS subjects (90%) demonstrating a bifidogenic response, in vivo. Principal coordinate analyses further showed a statistically significant shift in the microbiome in subjects fed GOS. Relative abundance of lactose fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus, were significantly increased in response to GOS. When dairy was introduced into the diet, lactose-fermenting Roseburia species increased from 36 to 66 days. The results indicated a definitive change in the fecal microbiome of lactose intolerant individuals, increasing lactose-metabolizing bacteria that were responsive to dietary adaptation to GOS and correlated with clinical outcomes toward lactose tolerance.
Sa1984 Influence of Intestinal Microbiome and Short Chain Fatty Acid on Metabolism in Type 2 Diabetes Patients Makoto Sasaki, Tomoya Sugiyama, Seiji Noguchi, Hiroki Kitahora, Akihiro Shimozato, Yoshiharu Yamaguchi, Kazunori Adachi, Noriko Okaniwa, Shigeki Goji, Atsushi Tanabe, Hisatsugu Noda, Yoshihiro Kondo, Yoshitsugi Ito, Shinya Izawa, Masahide Ebi, Naotaka Ogasawara, Yasushi Funaki, Kunio Kasugai Background & Aim: Evidence is accumulating that the intestinal microbiota, in addition to other major factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. We have reported gut dysbiosis in type 2 diabetes patients (BMC Gastroenterol. 2013;13:81). In this study, we examined relationship among gut microbiota, blood metabolism markers, dietary habits, and fecal short chain fatty acid in type 2 diabetes patients. Methods: Sixty type 2 diabetes patients (25 female and 35 men, mean age; 62.7 years old) were recruited in this study. Blood, fecal samples, and databased short food frequency questionnaires were analyzed. Results: Total energy intake was 1693 (948 - 2781) Kcal/day. Protein, fat, carbohydrate, and fiber intake were 55.0 (21.6 - 88.1) g, 42.3 (23.8 - 70.3) g, 244.7 (107.7 - 450.7) g, and 11.8 (6.4 - 21.2) g, respectively. Dietary habits (high protein, high fat, and high carbohydrate) were associated with increase of gut bacteria (Clostridium cluster XI, Clostridium cluster XI, and Clostridium cluster IV, respectively) (r= 0.363; R2=0.131; p=0.005, r=0.301; R2=0.091; p=0.021, and r=0.266; R2=0.071; p=0.042, respectively), and associated with decrease of gut bacteria ( Lactobacillales,Clostridium cluster IV, and Bifidobacterium, respectively) (r=−0.275; R2=0.076; p=0.035, r=−0.261; R2=0.068; p=0.046, and r=−0.420; R2=0.176; p=0.001, respectively). Dietary fiber, protein, fat, and carbohydrate amount had no influence to intestinal short chain fatty acid (SCFA), propionate,
AGA Abstracts
S-424