Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy in Rural Pakistan. Study Protocol for a Prospective, Longitudinal Observational Study.

Background: Nutritional status critically contributes to maternal and child morbidities and mortality. Undernutrition during pregnancy and preconception is linked to adverse pregnancy and birth outcomes and has downstream effects on the growth and development of children. The gut microbiome has a profound influence on the nutritional status of the host. Dysbiosis has emerged as a major factor in the development of malnutrition. This phenomenon is understudied in settings with a high prevalence of undernutrition, and further investigation is warranted to better understand such interactions. Methods: The study is a prospective, longitudinal observational study to investigate the impact and relationship between prokaryotic and eukaryotic microbes in the gut and their association with maternal health and birth outcomes among young women, 17-24 years of age in Matiari District, Pakistan. We aim to enroll 400 pregnant women with low and normal BMI at the time of recruitment (<16 weeks of gestation). Data collection includes demographics, morbidities, medication use, empowerment, dietary recall, and anthropometrics. Stool and blood specimens are collected at several time points for different laboratory assays. Discussion: Limited studies have examined the role of the microbiome in maternal health and birth outcomes where the prevalence of undernutrition is high. Here we aim to investigate the interplay of maternal and child undernutrition with the composition (diversity) and functionality of the gut microbiome and capture how it is influenced by environmental and genetic factors. Findings are expected to provide valuable insights into the understanding of undernutrition. Study registration: The study is registered with ClinicalTrials.gov Identifier: NCT05108675. Keywords: Maternal, Infant, BMI, Gut Microbiome, Dysbiosis, and Pregnancy Outcomes.

[1]  Jo-Anna B. Baxter,et al.  Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial , 2023, BMJ Open.

[2]  Jo-Anna B. Baxter,et al.  Dietary diversity and social determinants of nutrition among late adolescent girls in rural Pakistan , 2021, Maternal & child nutrition.

[3]  Jo-Anna B. Baxter,et al.  Characterizing Micronutrient Status and Risk Factors among Late Adolescent and Young Women in Rural Pakistan: A Cross-Sectional Assessment of the MaPPS Trial , 2021, Nutrients.

[4]  J. Parkinson,et al.  MetaPro: a scalable and reproducible data processing and analysis pipeline for metatranscriptomic investigation of microbial communities , 2021, bioRxiv.

[5]  K. Afsana,et al.  Maternal nutrition intervention and maternal complications in 4 districts of Bangladesh: A nested cross-sectional study , 2019, PLoS medicine.

[6]  Paul A. Harris,et al.  The REDCap consortium: Building an international community of software platform partners , 2019, J. Biomed. Informatics.

[7]  Julie M. Herlihy,et al.  Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study , 2018, The Lancet. Global health.

[8]  P. Webb,et al.  Biomarkers of maternal environmental enteric dysfunction are associated with shorter gestation and reduced length in newborn infants in Uganda , 2018, The American journal of clinical nutrition.

[9]  Jo-Anna B. Baxter,et al.  Effect of life skills building education and micronutrient supplements provided from preconception versus the standard of care on low birth weight births among adolescent and young Pakistani women (15–24 years): a prospective, population-based cluster-randomized trial , 2018, Reproductive Health.

[10]  Jo-Anna B. Baxter,et al.  Feasibility and effect of life skills building education and multiple micronutrient supplements versus the standard of care on anemia among non-pregnant adolescent and young Pakistani women (15–24 years): a prospective, population-based cluster-randomized trial , 2018, Reproductive Health.

[11]  J. Parkinson,et al.  Perilipin-2 modulates dietary fat-induced microbial global gene expression profiles in the mouse intestine , 2017, Microbiome.

[12]  C. Robert,et al.  Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics? , 2017, Front. Microbiol..

[13]  D. Raoult,et al.  Microbiota, obesity and malnutrition. , 2017, Microbial pathogenesis.

[14]  Jai K. Das,et al.  Evidence-based interventions for improvement of maternal and child nutrition in low-income settings: what's new? , 2017, Current opinion in clinical nutrition and metabolic care.

[15]  Aleksandra A. Kolodziejczyk,et al.  Dysbiosis and the immune system , 2017, Nature Reviews Immunology.

[16]  R. Britton,et al.  Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host , 2017, Gut microbes.

[17]  G. Kang,et al.  Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort , 2017, Journal of the Pediatric Infectious Diseases Society.

[18]  L. Ferrucci,et al.  Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation , 2017, EBioMedicine.

[19]  W. Petri,et al.  The Intestinal Bacterial Microbiome and E. histolytica Infection , 2016, Current Tropical Medicine Reports.

[20]  Michael J. Barratt,et al.  Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics , 2016, Science.

[21]  Guanhua Chen,et al.  PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances , 2016, Bioinform..

[22]  Sophie J. Weiss,et al.  Correlation detection strategies in microbial data sets vary widely in sensitivity and precision , 2016, The ISME Journal.

[23]  R. Haque,et al.  Role of the Gut Microbiota of Children in Diarrhea Due to the Protozoan Parasite Entamoeba histolytica , 2015, The Journal of infectious diseases.

[24]  M. Manco,et al.  NutricheQ Questionnaire assesses the risk of dietary imbalances in toddlers from 1 through 3 years of age , 2015, Food & nutrition research.

[25]  A. Simoes-Barbosa,et al.  The Interplay of Host Microbiota and Parasitic Protozoans at Mucosal Interfaces: Implications for the Outcomes of Infections and Diseases , 2015, PLoS neglected tropical diseases.

[26]  Forest Rohwer,et al.  Gut DNA viromes of Malawian twins discordant for severe acute malnutrition , 2015, Proceedings of the National Academy of Sciences.

[27]  Mark A. Miller,et al.  Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). , 2015, The Lancet. Global health.

[28]  R. Bell,et al.  Nutrient availability, the microbiome, and intestinal transport during pregnancy. , 2015, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[29]  Jean M. Macklaim,et al.  Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt , 2015, Applied and Environmental Microbiology.

[30]  S. Donaldson,et al.  Lung microbiota across age and disease stage in cystic fibrosis , 2015, Scientific Reports.

[31]  J. Berkley,et al.  Environmental Enteric Dysfunction: An Overview , 2015, Food and nutrition bulletin.

[32]  Mehdi Layeghifard,et al.  Seasonal community succession of the phyllosphere microbiome. , 2015, Molecular plant-microbe interactions : MPMI.

[33]  José Villar,et al.  International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project , 2014, The Lancet.

[34]  Qunyuan Zhang,et al.  Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children , 2014, Nature.

[35]  J. Round,et al.  Defining dysbiosis and its influence on host immunity and disease , 2014, Cellular microbiology.

[36]  M. Ngari,et al.  Childhood Malnutrition: Toward an Understanding of Infections, Inflammation, and Antimicrobials , 2014, Food and nutrition bulletin.

[37]  Zhuowen Tu,et al.  Similarity network fusion for aggregating data types on a genomic scale , 2014, Nature Methods.

[38]  B. Striepen Parasitic infections: Time to tackle cryptosporidiosis , 2013, Nature.

[39]  M. Silverberg,et al.  Characterization of the Gut-Associated Microbiome in Inflammatory Pouch Complications Following Ileal Pouch-Anal Anastomosis , 2013, PloS one.

[40]  W. Fawzi,et al.  Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis , 2013, The Lancet.

[41]  Patrick Webb,et al.  Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? , 2013, The Lancet.

[42]  R. Martorell,et al.  Maternal and child undernutrition and overweight in low-income and middle-income countries , 2013, The Lancet.

[43]  Inacio Mandomando,et al.  Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study , 2013, The Lancet.

[44]  L. Ursell,et al.  Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor , 2013, Science.

[45]  Shihab U. Sobuz,et al.  A Laboratory-Developed TaqMan Array Card for Simultaneous Detection of 19 Enteropathogens , 2012, Journal of Clinical Microbiology.

[46]  L. T. Angenent,et al.  Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy , 2012, Cell.

[47]  R. Martorell,et al.  Effect of women's nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review. , 2012, Paediatric and perinatal epidemiology.

[48]  G. Zimet,et al.  Multidimensional Scale of Perceived Social Support , 2011 .

[49]  L. Poston,et al.  Micronutrients in pregnancy: current knowledge and unresolved questions. , 2011, Clinical nutrition.

[50]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[51]  Martin Hartmann,et al.  Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities , 2009, Applied and Environmental Microbiology.

[52]  P. Harris,et al.  Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support , 2009, J. Biomed. Informatics.

[53]  D. Fone,et al.  Teenage pregnancy: who suffers? , 2008, Archives of Disease in Childhood.

[54]  R. Knight,et al.  Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex , 2008, Nature Methods.

[55]  M. Rahu,et al.  Is a poor pregnancy outcome related to young maternal age? A study of teenagers in Estonia during the period of major socio-economic changes (from 1992 to 2002). , 2007, European journal of obstetrics, gynecology, and reproductive biology.

[56]  T. Roseboom,et al.  The Dutch famine and its long-term consequences for adult health. , 2006, Early human development.

[57]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[58]  H. Leclerc,et al.  Microbial Agents Associated with Waterborne Diseases , 2002, Critical reviews in microbiology.

[59]  A. Tomkins,et al.  Nutrition and maternal morbidity and mortality , 2001, British Journal of Nutrition.

[60]  D. Sellen,et al.  Genetics of Criminal and Antisocial Behaviour. Ciba Foundation Symposium 194. Pp. 283. Edited by G. R. Bock & J. A. Goode. (Wiley, Chichester, 1996.) £50.00. , 1998, Journal of Biosocial Science.

[61]  D J Barker,et al.  Fetal origins of coronary heart disease , 1995, BMJ.

[62]  A. R. Frisancho Physical Status: The Use and Interpretation of Anthropometry , 1996, The American Journal of Clinical Nutrition.

[63]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[64]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[65]  Julie M. Herlihy,et al.  Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study , 2019 .

[66]  Data4Diets: Building Blocks for Diet-related Food Security Analysis , 2019 .

[67]  E. Ferguson,et al.  An interactive 24-hour recall for assessing the adequacyof iron and zinc intakes in developing countries. , 2008 .

[68]  J. Harding,et al.  The nutritional basis of the fetal origins of adult disease. , 2001, International journal of epidemiology.