Ayodeji Awoyemi1, Marius Trøseid2, Harald Arnesen3, Svein Solheim4, Ingebjørg Seljeflot3. 1. Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318, Oslo, Norway. Electronic address: a.o.awoyemi@medisin.uio.no. 2. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318, Oslo, Norway. 3. Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318, Oslo, Norway. 4. Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, P.O. Box 4956 Nydalen, N-0424, Oslo, Norway.
Abstract
BACKGROUND & AIMS: Dysbiosis of the gut microbiota is associated with increased levels of circulating lipopolysaccharide (LPS) and subsequent activation of systemic inflammation. Diet is an important modulator of the gut microbiome. We aimed to investigate whether circulating markers of gut-related inflammation, LPS binding protein (LBP) and soluble CD14 (sCD14) can be modulated by n-3 PUFA supplementation and/or diet counselling, and whether these markers are related to cardiovascular (CV) outcome. METHODS:484 men aged 65-75 years, at high CV-risk, were included and randomized in a 2 × 2 factorial design to 36-month intervention with dietary counselling, n-3 PUFA supplementation, or both. N-3 PUFA supplementation was placebo-controlled. ELISAs were used for determination of the biomarkers measured at baseline and study-end. A composite endpoint was defined as new CV-events and CV-mortality after 36 months. RESULTS: There were no significant differences in changes of either LBP or sCD14 in the intervention groups compared to their respective controls (n-3 PUFA vs. placebo: p = 0.58, p = 0.15, diet vs. no-diet: p = 0.53, p = 0.59, respectively). The group with LBP levels above median had about 2-fold unadjusted risk of suffering an endpoint compared to the group below (HR 2.22, 95% CI 1.25-3.96; p = 0.01). A similar tendency was seen for sCD14 (HR 1.72, 95% CI 0.97-3.03; p = 0.06). After adjusting for covariates, LBP remained significantly associated with a two-fold CV-risk, whereas sCD14 gained statistical significance, however, lost when hsCRP was added to the model. CONCLUSIONS: In our population, markers of gut-related inflammation associated with 36-month CV outcome. However, neither n-3 PUFA nor diet intervention had an effect on these markers.
RCT Entities:
BACKGROUND & AIMS: Dysbiosis of the gut microbiota is associated with increased levels of circulating lipopolysaccharide (LPS) and subsequent activation of systemic inflammation. Diet is an important modulator of the gut microbiome. We aimed to investigate whether circulating markers of gut-related inflammation, LPS binding protein (LBP) and soluble CD14 (sCD14) can be modulated by n-3 PUFA supplementation and/or diet counselling, and whether these markers are related to cardiovascular (CV) outcome. METHODS: 484 men aged 65-75 years, at high CV-risk, were included and randomized in a 2 × 2 factorial design to 36-month intervention with dietary counselling, n-3 PUFA supplementation, or both. N-3 PUFA supplementation was placebo-controlled. ELISAs were used for determination of the biomarkers measured at baseline and study-end. A composite endpoint was defined as new CV-events and CV-mortality after 36 months. RESULTS: There were no significant differences in changes of either LBP or sCD14 in the intervention groups compared to their respective controls (n-3 PUFA vs. placebo: p = 0.58, p = 0.15, diet vs. no-diet: p = 0.53, p = 0.59, respectively). The group with LBP levels above median had about 2-fold unadjusted risk of suffering an endpoint compared to the group below (HR 2.22, 95% CI 1.25-3.96; p = 0.01). A similar tendency was seen for sCD14 (HR 1.72, 95% CI 0.97-3.03; p = 0.06). After adjusting for covariates, LBP remained significantly associated with a two-fold CV-risk, whereas sCD14 gained statistical significance, however, lost when hsCRP was added to the model. CONCLUSIONS: In our population, markers of gut-related inflammation associated with 36-month CV outcome. However, neither n-3 PUFA nor diet intervention had an effect on these markers.
Authors: Carlos Jiménez-Cortegana; Pedro Iglesias; Josep Ribalta; Teresa Vilariño-García; Laura Montañez; Francisco Arrieta; Manuel Aguilar; Santiago Durán; Juan C Obaya; Antonio Becerra; Juan Pedro-Botet; Víctor Sánchez-Margalet Journal: Nutrients Date: 2021-11-19 Impact factor: 5.717