Interactions between the Gut Microbiome and Mucosal Immunoglobulins A, M, and G in the Developing Infant Gut

ABSTRACT Interactions between the gut microbiome and immunoglobulin A (IgA) in the gut during infancy are important for future health. IgM and IgG are also present in the gut; however, their interactions with the microbiome in the developing infant remain to be characterized. Using stool samples sampled 15 times in infancy from 32 healthy subjects at 4 locations in 3 countries, we characterized patterns of microbiome development in relation to fecal levels of IgA, IgG, and IgM. For 8 infants from a single location, we used fluorescence-activated cell sorting of microbial cells from stool by Ig-coating status over 18 months. We used 16S rRNA gene profiling on full and sorted microbiomes to assess patterns of antibody coating in relation to age and other factors. All antibodies decreased in concentration with age but were augmented by breastmilk feeding regardless of infant age. Levels of IgA correlated with relative abundances of operational taxonomic units (OTUs) belonging to the Bifidobacteria and Enterobacteriaceae, which dominated the early microbiome, and IgG levels correlated with Haemophilus. The diversity of Ig-coated microbiota was influenced by breastfeeding and age. IgA and IgM coated the same microbiota, which reflected the overall diversity of the microbiome, while IgG targeted a different subset. Blautia generally evaded antibody coating, while members of the Bifidobacteria and Enterobacteriaceae were high in IgA/M. IgA/M displayed similar dynamics, generally coating the microbiome proportionally, and were influenced by breastfeeding status. IgG only coated a small fraction of the commensal microbiota and differed from the proportion targeted by IgA and IgM. IMPORTANCE Antibodies are secreted into the gut and attach to roughly half of the trillions of bacterial cells present. When babies are born, the breastmilk supplies these antibodies until the baby’s own immune system takes over this task after a few weeks. The vast majority of these antibodies are IgA, but two other types, IgG and IgM, are also present in the gut. Here, we ask if these three different antibody types target different types of bacteria in the infant gut as the infant develops from birth to 18 months old and how patterns of antibody coating of bacteria change with age. In this study of healthy infant samples over time, we found that IgA and IgM coat the same bacteria, which are generally representative of the diversity present, with a few exceptions that were more or less antibody coated than expected. IgG coated a separate suite of bacteria. These results provide a better understanding of how these antibodies interact with the developing infant gut microbiome.

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Interactions between the gut microbiome and mucosal immunoglobulins A, M and G in the developing infant gut

10.1101/637959 ◽

2019 ◽

Author(s):

Anders Janzon ◽

Julia K. Goodrich ◽

Omry Koren ◽

Jillian L. Waters ◽

Ruth E. Ley ◽

...

Keyword(s):

Gut Microbiome ◽

Gene Profiling ◽

Secretory Iga ◽

Rrna Gene ◽

List Type ◽

Microbial Cells ◽

New Findings ◽

Infant Gut Microbiome ◽

Antibody Coating ◽

Microbiome Development

AbstractObjectiveInteractions between the gut microbiome and immunoglobulin (Ig) A in infancy are important for future health. IgM and IgG are also present, however, their interactions with the microbiome in the developing infant are less understood.DesignWe employed stool samples sampled 15 times in infancy from 32 healthy subjects at 4 locations in 3 countries (from the TEDDY study). We characterized patterns of microbiome development in relation to levels of IgA, IgG and IgM. For 8 infants from a single location, we FACS-sorted microbial cells from stool by Ig status. We used 16S rRNA gene profiling on full and sorted microbiomes to assess patterns of antibody coating in relation to age and other factors.ResultsAll antibodies decreased in concentration with age, but were augmented by breastmilk feeding regardless of infant age. Levels of IgA correlated with the relative abundances of OTUs belonging to the Bifidobacteria and Enterobacteriaceae, which dominated the early microbiome, and IgG levels correlated with Haemophilus. The diversity of Ig-coated microbiota was influenced by breastfeeding and age, but birth mode. IgA and IgM coated the same microbiota, while IgG targeted a different subset. Blautia generally evaded antibody coating, while members of the Bifidobacteria and Enterobacteriaceae were high in IgA/M.ConclusionIgA/M have similar dynamics with respect to microbiome development with age, and their interactions with the microbiome are influenced by breastfeeding status. IgG generally does not coat the commensal microbiota.SummaryWhat is already known on this subject?Secretory IgA coats ~50% of microbiota in the gutIgM and IgG are less prevalent and coat a lower fraction in the adult, dynamics in the infant gut are not well characterized.Breastmilk is a source of IgA to the infant gut and decreases with time.IgA coating of microbial cells in infant gut microbiome decreases over time.What are the new findings?Breastfeeding augments the IgA coating of the microbiome at all ages.IgA and IgM coat many of the same cells, whereas few are coated by IgG alone.Bifidobacteria, Enterobacteriaceae, Ruminococcus gnavus are enriched in IgA/M-coated cell fraction, Blautia is enriched in uncoated fraction.IgG levels correlated with Haemophilus.How might it impact on clinical practice in the foreseeable future?Ig-coated fraction of the gut microbiome could serve as a useful tool for tracking development of the infant gut microbiome, and/or identifying aberrations to immune sensing of the microbiome.

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The association between the maternal diet and the maternal and infant gut microbiome: a systematic review

British Journal Of Nutrition ◽

10.1017/s0007114520000847 ◽

2020 ◽

pp. 1-29 ◽

Cited By ~ 8

Author(s):

Siofra E. Maher ◽

Eileen C. O’Brien ◽

Rebecca L. Moore ◽

David F. Byrne ◽

Aisling A. Geraghty ◽

...

Keyword(s):

Microbial Diversity ◽

Gut Microbiome ◽

Dietary Intervention ◽

Maternal Diet ◽

Rrna Gene ◽

High Fat ◽

High Fat Diets ◽

Culture Independent ◽

Infant Gut Microbiome ◽

Fat Diets

Abstract During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.

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Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants

Clinical Infectious Diseases ◽

10.1093/cid/ciy882 ◽

2018 ◽

Vol 69 (2) ◽

pp. 268-277 ◽

Cited By ~ 21

Author(s):

S Graspeuntner ◽

S Waschina ◽

S Künzel ◽

N Twisselmann ◽

T K Rausch ◽

...

Keyword(s):

Preterm Infants ◽

Gut Microbiome ◽

Late Onset ◽

Anaerobic Bacteria ◽

Gene Profiling ◽

Rrna Gene ◽

Coagulase Negative Staphylococci ◽

Fermentation Products ◽

Gut Dysbiosis ◽

Late Onset Sepsis

Abstract Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

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Gut microbiota features of the geographically diverse Indian population

10.1101/478586 ◽

2018 ◽

Cited By ~ 1

Author(s):

Sudarshan A. Shetty

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Indian Population ◽

Geographic Location ◽

Population Level ◽

Gene Profiling ◽

Rrna Gene ◽

Base Line ◽

Microbiome Composition ◽

And Function

AbstractPopulation-level microbial profiling allows for identifying the overarching features of the microbiome. Knowledge of population specific base-line gut microbiome features is important due to the widely reported impact of geography, lifestyle and dietary patterns on the microbiome composition, structure and function. Here, the gut microbiota of more than 1000 subjects across the length and breadth of India is presented. The publicly available 16S rRNA gene profiling data of faecal microbiota from the Landscape Of Gut Microbiome - Pan-India Exploration (LogMPIE) study representing 14 major cities, covering populations from northern, southern, eastern and western part of India analyzed. Majority of the dominant OTUs belonged to the Firmicutes, Bacteroidetes and Proteobacteria phyla. The rarer fraction was comprised of OTUs mainly from the phyla Verrucomicrobia and Spirochaetes. The median core size was estimated to consist of 12 OTUs (>80% prevalence) dominated by representing genera Prevotella, Faecalibacterium, Bacteroides, Roseburia, Megasphaera, Eubacterium and Gemmiger. Geographic location explained majority of the variation in the gut microbiota community structure. The observations of the present study support the previous reports of Prevotella dominance in the Indian population. The Prevotella/Bacteroides ratio was high for the overall population irrespective of geographic location and did not correlate with BMI or age of the participants. Despite a rapid transition towards a western lifestyle, high prevalence of Treponema in the Indian gut microbiota suggests that the urban population still harbors signatures of the traditional gut microbiome. The results presented here improve the knowledge of baseline microbiota in the Indian population across the length and breadth of the country. This study provides a base for future studies which need to incorporate numerous other confounding factors and their impact on the observed characteristics of the Indian gut microbiome.

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Complementary Food Ingredients Alter Infant Gut Microbiome Composition and Metabolism In Vitro

Microorganisms ◽

10.3390/microorganisms9102089 ◽

2021 ◽

Vol 9 (10) ◽

pp. 2089

Author(s):

Shanthi G. Parkar ◽

Doug I. Rosendale ◽

Halina M. Stoklosinski ◽

Carel M. H. Jobsis ◽

Duncan I. Hedderley ◽

...

Keyword(s):

Gut Microbiome ◽

Milk Powder ◽

Free Water ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Water Control ◽

Food Ingredients ◽

Microbiome Composition ◽

Infant Gut Microbiome

We examined the prebiotic potential of 32 food ingredients on the developing infant microbiome using an in vitro gastroileal digestion and colonic fermentation model. There were significant changes in the concentrations of short-chain fatty-acid metabolites, confirming the potential of the tested ingredients to stimulate bacterial metabolism. The 16S rRNA gene sequencing for a subset of the ingredients revealed significant increases in the relative abundances of the lactate- and acetate-producing Bifidobacteriaceae, Enterococcaceae, and Lactobacillaceae, and lactate- and acetate-utilizing Prevotellaceae, Lachnospiraceae, and Veillonellaceae. Selective changes in specific bacterial groups were observed. Infant whole-milk powder and an oat flour enhanced Bifidobacteriaceae and lactic acid bacteria. A New Zealand-origin spinach powder enhanced Prevotellaceae and Lachnospiraceae, while fruit and vegetable powders increased a mixed consortium of beneficial gut microbiota. All food ingredients demonstrated a consistent decrease in Clostridium perfringens, with this organism being increased in the carbohydrate-free water control. While further studies are required, this study demonstrates that the selected food ingredients can modulate the infant gut microbiome composition and metabolism in vitro. This approach provides an opportunity to design nutrient-rich complementary foods that fulfil infants’ growth needs and support the maturation of the infant gut microbiome.

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High royal jelly production does not impact the gut microbiome of honey bees

Animal Microbiome ◽

10.1186/s42523-021-00124-1 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Megan E. Damico ◽

Olav Rueppell ◽

Zack Shaffer ◽

Bin Han ◽

Kasie Raymann

Keyword(s):

Honey Bee ◽

Gut Microbiome ◽

Honey Bees ◽

Urban Areas ◽

Royal Jelly ◽

Gene Profiling ◽

Rrna Gene ◽

Pollination Services ◽

Bacterial Composition ◽

Neurological Differences

Abstract Background Honey bees are not only essential for pollination services, but are also economically important as a source of hive products (e.g., honey, royal jelly, pollen, wax, and propolis) that are used as foods, cosmetics, and alternative medicines. Royal jelly is a popular honey bee product with multiple potential medicinal properties. To boost royal jelly production, a long-term genetic selection program of Italian honey bees (ITBs) in China has been performed, resulting in honey bee stocks (here referred to as RJBs) that produce an order of magnitude more royal jelly than ITBs. Although multiple studies have investigated the molecular basis of increased royal jelly yields, one factor that has not been considered is the role of honey bee-associated gut microbes. Results Based on the behavioral, morphological, physiological, and neurological differences between RJBs and ITBs, we predicted that the gut microbiome composition of RJBs bees would differ from ITBs. To test this hypothesis, we investigated the bacterial composition of RJB and ITB workers from an urban location and RJBs from a rural location in China. Based on 16S rRNA gene profiling, we did not find any evidence that RJBs possess a unique bacterial gut community when compared to ITBs. However, we observed differences between honey bees from the urban versus rural sites. Conclusions Our results suggest that the environmental factors rather than stock differences are more important in shaping the bacterial composition in honey bee guts. Further studies are needed to investigate if the observed differences in relative abundance of taxa between the urban and rural bees correspond to distinct functional capabilities that impact honey bee health. Because the lifestyle, diet, and other environmental variables are different in rural and urban areas, controlled studies are needed to determine which of these factors are responsible for the observed differences in gut bacterial composition between urban and rural honeybees.

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Investigating colonization patterns of the infant gut microbiome during the introduction of solid food and weaning from breastmilk: A cohort study protocol

PLoS ONE ◽

10.1371/journal.pone.0248924 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248924

Author(s):

Sara Dizzell ◽

Jennifer C. Stearns ◽

Jenifer Li ◽

Niels van Best ◽

Liene Bervoets ◽

...

Keyword(s):

Gut Microbiome ◽

Infant Nutrition ◽

Solid Food ◽

Gene Profiling ◽

Rrna Gene ◽

Birth Cohorts ◽

Solid Foods ◽

Infancy And Early Childhood ◽

And Function ◽

The Impact

The first exposures to microbes occur during infancy and it is suggested that this initial colonization influences the adult microbiota composition. Despite the important role that the gut microbiome may have in health outcomes later in life, the factors that influence its development during infancy and early childhood have not been characterized fully. Guidelines about the introduction of solid foods and cessation of breastfeeding, which is thought to have a significant role in the transition to a more adult-like microbiota, are not based on microbiome research. There is even less understanding of approaches used to transition to solid food in the preterm population. The purpose of this study is to identify the impact of early life dietary events on gut microbiome community structures and function among infants born at term and pre-term. We plan to prospectively monitor the gut microbiome of infants during two critical timepoints in microbial development: the introduction of solid foods and cessation from breastmilk. A total of 35 participants from three primary observational birth cohorts (two full-term cohorts and one pre-term cohort) will be enrolled in this sub-study. Participants will be asked to collect stool samples and fill out a study diary before, during and after the introduction of solids and again during weaning from breastmilk. We will use frequent fecal sampling analyzed using 16S rRNA gene profiling, metagenomics, metabolomics, and targeted bacterial culturing to identify and characterize the microbial communities, as well as provide insight into the phenotypic characteristics and functional capabilities of the microbes present during these transitional periods of infancy. This study will provide a comprehensive approach to detailing the effects of dietary transition from breastmilk to a more adult-like solid food diet on the microbiome and in doing so will contribute to evidence-based infant nutrition guidance.

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Urinary TMAO Levels Are Associated with the Taxonomic Composition of the Gut Microbiota and with the Choline TMA-Lyase Gene (cutC) Harbored by Enterobacteriaceae

Nutrients ◽

10.3390/nu12010062 ◽

2019 ◽

Vol 12 (1) ◽

pp. 62 ◽

Cited By ~ 6

Author(s):

Alessandro Dalla Via ◽

Giorgio Gargari ◽

Valentina Taverniti ◽

Greta Rondini ◽

Ilaria Velardi ◽

...

Keyword(s):

Gut Microbiota ◽

Method Development ◽

Ultra Performance Liquid Chromatography ◽

Taxonomic Composition ◽

Gene Profiling ◽

Rrna Gene ◽

Operational Taxonomic Units ◽

Two Factors ◽

Polymerase Chain ◽

Dietary Choline

Gut microbiota metabolization of dietary choline may promote atherosclerosis through trimethylamine (TMA), which is rapidly absorbed and converted in the liver to proatherogenic trimethylamine-N-oxide (TMAO). The aim of this study was to verify whether TMAO urinary levels may be associated with the fecal relative abundance of specific bacterial taxa and the bacterial choline TMA-lyase gene cutC. The analysis of sequences available in GenBank grouped the cutC gene into two main clusters, cut-Dd and cut-Kp. A quantitative real-time polymerase chain reaction (qPCR) protocol was developed to quantify cutC and was used with DNA isolated from three fecal samples collected weekly over the course of three consecutive weeks from 16 healthy adults. The same DNA was used for 16S rRNA gene profiling. Concomitantly, urine was used to quantify TMAO by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). All samples were positive for cutC and TMAO. Correlation analysis showed that the cut-Kp gene cluster was significantly associated with Enterobacteriaceae. Linear mixed models revealed that urinary TMAO levels may be predicted by fecal cut-Kp and by 23 operational taxonomic units (OTUs). Most of the OTUs significantly associated with TMAO were also significantly associated with cut-Kp, confirming the possible relationship between these two factors. In conclusion, this preliminary method-development study suggests the existence of a relationship between TMAO excreted in urine, specific fecal bacterial OTUs, and a cutC subgroup ascribable to the choline-TMA conversion enzymes of Enterobacteriaceae.

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Maternal group B Streptococcus and the infant gut microbiota

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415001361 ◽

2015 ◽

Vol 7 (1) ◽

pp. 45-53 ◽

Cited By ~ 16

Author(s):

A. E. Cassidy-Bushrow ◽

A. Sitarik ◽

A. M. Levin ◽

S. V. Lynch ◽

S. Havstad ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Negative Binomial ◽

Group B Streptococcus ◽

Illumina Miseq ◽

Rrna Gene ◽

Adult Disease ◽

Gut Colonization ◽

Infant Gut Microbiome ◽

Group B

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant’s diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R2=0.008, P=0.008; Unweighted UniFrac R2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

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Prospective associations of the infant gut microbiome and microbial function with social behaviors related to autism at age 3 years

Scientific Reports ◽

10.1038/s41598-020-72386-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Hannah E. Laue ◽

Susan A. Korrick ◽

Emily R. Baker ◽

Margaret R. Karagas ◽

Juliette C. Madan

Keyword(s):

Gut Microbiome ◽

Social Behaviors ◽

Autism Spectrum ◽

Rrna Gene ◽

Social Responsiveness ◽

Metagenomic Sequencing ◽

Shotgun Metagenomic Sequencing ◽

Infant Gut Microbiome ◽

One Year ◽

And Function

Abstract The hypothesized link between gut bacteria and autism spectrum disorder (ASD) has been explored through animal models and human studies with microbiome assessment after ASD presentation. We aimed to prospectively characterize the association between the infant/toddler gut microbiome and ASD-related social behaviors at age 3 years. As part of an ongoing birth cohort gut bacterial diversity, structure, taxa, and function at 6 weeks (n = 166), 1 year (n = 158), 2 years (n = 129), and 3 years (n = 140) were quantified with 16S rRNA gene and shotgun metagenomic sequencing (n = 101 six weeks, n = 103 one year). ASD-related social behavior was assessed at age 3 years using Social Responsiveness Scale (SRS-2) T-scores. Covariate-adjusted linear and permutation-based models were implemented. Microbiome structure at 1 year was associated with SRS-2 total T-scores (p = 0.01). Several taxa at 1, 2, and 3 years were associated with SRS-2 performance, including many in the Lachnospiraceae family. Higher relative abundance of Adlercreutzia equolifaciens and Ruminococcus torques at 1 year related to poorer SRS-2 performance. Two functional pathways, l-ornithine and vitamin B6 biosynthesis, were associated with better social skills at 3 years. Our results support potential associations between early-childhood gut microbiome and social behaviors. Future mechanistic studies are warranted to pinpoint sensitive targets for intervention.

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