The Developmental Ecology of the Infant Gut Microbiome Restricted; Files Only

Sheets, Gabriela Mandel Maíz (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/4t64gn875?locale=en
Published

Abstract

Introduction: Within the human intestinal tract lives a complex and dynamic community of microorganisms, called the intestinal microbiome. Human behavior and ecology play central roles in shaping this resident community during development. The microbiome assembles anew with each host generation, and given its critical role in human somatic, immune and metabolic development, natural selection likely has conserved mechanisms for the intergenerational transfer such that infants receive an optimal supply of human-adapted microbiota. Research shows that contemporary birthing methods and feeding practices disrupt the successional inheritance during early life, yet little is known about how diverse developmental ecologies influence the infant gut microbiome.

This dissertation is a biocultural, multi-disciplinary, and longitudinal exploration of microbial development within a semi-rural Salvadoran population. Assuming a developmental ecology framework, I probe the broader socio-political and economic processes acting upon infant microbial ontogeny via proximal developmental ecologies that mediate exposure. I test two propositions: First, the ontogeny of the microbiome requires an initial vertically selected microbiota, and with the continued protection of breastmilk, it increasingly demands a more diverse, horizontally-transmitted microbial assortment. Second, contemporary behaviors can interrupt the timeline of vertical and horizontal exposures, resulting in altered microbial assembly, growth and health outcomes.

Methods: 71 caretaker-infant pairs were recruited and followed for 12 months. Three study phases included collection of interviews, 24-hour dietary recalls, health histories, anthropometrics, participant observation, and fecal samples. Fecal samples were frozen (-20oC) and transported to CU Boulder for 16S rRNA sequencing.

Results: Factors influencing the vertical transmission (birth-mode and early feeding), and those influencing horizontal transmission (childcare networks, gendered labor patterns, and household microbial ecologies) significantly affected infant microbial diversity, stability and composition in the first year. Altered colonization patterns were associated with distinct growth phenotypes and health outcomes.

Discussion: Through comparative analyses and the development of a tri-fold, microbe-host-ecology integrative model, I explored the timeline of vertical and horizontal exposures, identified ontological microbial variations, and assessed functional relationships with health and growth outcomes. Novel analytic methods were developed to identify intra-population parameters of age-dependent "healthy" microbiome development. Recommendations for microbial interventions and policy-makers were made to support a holistic and life-course view of humans and their microbial partners.

Table of Contents

Table of Contents

Acknowledgements. i

Dedicado a Niña Ana Carmen Díaz de Marroquín (1957-2016). iii

Table of Contents.

Table of Figures.

Table of Tables.

Index of acronyms.

Social and Ecological Indexes.

Early feeding.

Birth mode. 15

Sub groups of early feeding and birth mode.

Growth.

Microbial metrics .

Terms.

Chapter 1: Introduction. 1

Human-associated microbial development. 4

Vertical colonization patterns. 4

Horizontal exposures and colonization patterns. 7

A political history of El Salvador and Joya de Cerén. 9

Community setting. 15

From co-op to milpa to market: a socio-economic history of Joya de Cerén. 16

Economic transition and gendered labor markets. 20

The social realm. 27

Selection of study site. 29

Study population and methods. 31

Roadmap of dissertation. 35

Works Cited. 38

Chapter 2: The Early Development of the Infant Microbiome in a Semi-rural Salvadoran Population 46

Introduction. 46

Study population and context. 49

Research Questions and Hypotheses. 50

Methods. 52

Results. 55

Discussion. 76

Works Cited. 89

Chapter 3: A Developmental Ecology of the Infant Gut Microbiome. 97

Introduction. 97

Section I: Study Population and microbial ecology contextualized. 101

Household construction; then and now. 101

Household construction and child care networks. 104

The demographic transition and thinning child care networks. 105

Gendered labor patterns, the household and childcare networks. 106

Increased paternal participation. 108

Socioeconomic status. 109

Low SES households (39.4% of sample) 111

Middle SES household (26.8% of sample) 113

High SES households (29.6% of sample) 115

Microbial Ecology and the HMEI Index. 117

Low HMEI Households (17% of sample) 120

Middle HMEI Households (43% of sample) 121

High HMEI households (38% of sample) 122

Early Feeding Ecology. 122

Beliefs about appropriate infant feeding. 123

Infant feeding practices. 126

Section II: Research questions and hypotheses. 131

Methods. 133

Results. 137

Discussion. 147

Works Cited. 153

Chapter 4: Infant Growth, Health and the Gut Microbiome. 157

Introduction. 157

Section I: Human Growth, Development, and the Infant Gut Microbiome. 160

Selective pressures on human infant growth. 160

Early immunity and growth impairment. 165

Defining growth and development. 167

The social determinants of growth. 169

Microbial correlates of growth. 170

Research questions and hypotheses. 179

Section II: Case study of a Salvadoran Infant Population. 181

Study population and setting. 181

Methods. 184

Results. 188

Discussion. 205

Works Cited. 215

Chapter 5: Functional Index of Relevant Taxa. 226

Introduction. 226

Akkermansia. 227

Study findings. 229

Key words: 230

Bacteroides. 231

Study findings. 233

Key words. 234

Bifidobacteria. 234

Study findings. 237

Key words. 238

Blautia. 239

Study findings. 240

Key words. 242

Clostridia. 242

Study findings. 243

Key words. 243

Clostridiales (order) 244

Study Findings. 244

Key words. 245

Corynebacterium.. 245

Study findings. 247

Key words. 247

Enterobacteriaceae (family) 247

Study findings. 250

Key words. 251

Enterococcus. 252

Study findings. 254

Key words. 255

Faecalibacterium.. 255

Study findings. 258

Key words. 262

Lachnospiraceae (family) 262

Study findings. 263

Key words. 265

Lactobacillus. 265

Study findings. 267

Key words. 269

Megasphaera. 270

Study findings. 271

Key words. 271

Prevotella. 272

Study findings. 273

Key words. 275

Roseburia. 276

Study findings. 276

Key words. 277

Rothia. 277

Study findings. 278

Key words. 278

Ruminococcus. 278

Study findings. 279

Key words. 281

Staphylococcus. 281

Study findings. 283

Key words. 284

Streptococci 284

Study findings. 285

Key words. 286

Veillonella. 286

Study findings. 287

Key words. 289

Discussion. 289

Other charts and reference materials: 295

Quick reference microbial summary: 295

Patterns of colonization: 295

Additional figures. 297

Works Cited. 299

Chapter 6: Conclusion. 314

Limitations. 336

Implications and recommendations for policy. 339

Future research. 345

Conclusion. 347

Works Cited. 349


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