Victoria Gershuni1, Yun Li2, Michal Elovitz3, Hongzhe Li2, Gary D Wu4, Charlene W Compher5. 1. Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Maternal and Fetal Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 5. School of Nursing, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
BACKGROUND: A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet-microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States. OBJECTIVES: In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB. METHODS: The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon's rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. β-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis. RESULTS: A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01), with greater DHA (22:6n-3) and EPA (20:5n-3) in cases [false discovery rate (FDR) < 0.2]. The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. Dietary saturated fat (primarily palmitate) intake was greater in cases (31.38 ± 7.37 compared with 26.08 ± 8.62 g, P = 0.045) and was positively correlated with fecal DHA and EPA (P < 0.05). CONCLUSIONS: Reduced α-diversity of the gut microbiota and higher excretion of omega-3 (n-3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation.
BACKGROUND: A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet-microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States. OBJECTIVES: In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB. METHODS: The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon's rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. β-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis. RESULTS: A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01), with greater DHA (22:6n-3) and EPA (20:5n-3) in cases [false discovery rate (FDR) < 0.2]. The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. Dietary saturated fat (primarily palmitate) intake was greater in cases (31.38 ± 7.37 compared with 26.08 ± 8.62 g, P = 0.045) and was positively correlated with fecal DHA and EPA (P < 0.05). CONCLUSIONS: Reduced α-diversity of the gut microbiota and higher excretion of omega-3 (n-3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation.
Authors: Helle Krogh Pedersen; Valborg Gudmundsdottir; Henrik Bjørn Nielsen; Tuulia Hyotylainen; Trine Nielsen; Benjamin A H Jensen; Kristoffer Forslund; Falk Hildebrand; Edi Prifti; Gwen Falony; Emmanuelle Le Chatelier; Florence Levenez; Joel Doré; Ismo Mattila; Damian R Plichta; Päivi Pöhö; Lars I Hellgren; Manimozhiyan Arumugam; Shinichi Sunagawa; Sara Vieira-Silva; Torben Jørgensen; Jacob Bak Holm; Kajetan Trošt; Karsten Kristiansen; Susanne Brix; Jeroen Raes; Jun Wang; Torben Hansen; Peer Bork; Søren Brunak; Matej Oresic; S Dusko Ehrlich; Oluf Pedersen Journal: Nature Date: 2016-07-13 Impact factor: 49.962
Authors: Gary D Wu; Jun Chen; Christian Hoffmann; Kyle Bittinger; Ying-Yu Chen; Sue A Keilbaugh; Meenakshi Bewtra; Dan Knights; William A Walters; Rob Knight; Rohini Sinha; Erin Gilroy; Kernika Gupta; Robert Baldassano; Lisa Nessel; Hongzhe Li; Frederic D Bushman; James D Lewis Journal: Science Date: 2011-09-01 Impact factor: 47.728
Authors: Linda Englund-Ögge; Anne Lise Brantsæter; Verena Sengpiel; Margareta Haugen; Bryndis Eva Birgisdottir; Ronny Myhre; Helle Margrete Meltzer; Bo Jacobsson Journal: BMJ Date: 2014-03-04
Authors: Siddhartha Mandal; Keith M Godfrey; Daniel McDonald; Will V Treuren; Jørgen V Bjørnholt; Tore Midtvedt; Birgitte Moen; Knut Rudi; Rob Knight; Anne Lise Brantsæter; Shyamal D Peddada; Merete Eggesbø Journal: Microbiome Date: 2016-10-19 Impact factor: 14.650
Authors: Emma Ronde; Irwin K M Reiss; Thomas Hankemeier; Tim G De Meij; Nina Frerichs; Sam Schoenmakers Journal: Front Endocrinol (Lausanne) Date: 2021-09-06 Impact factor: 5.555