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.

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

ObjectiveInteractions 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.

Mouse and human HSPC immobilization in liquid culture by CD43- or CD44-antibody coating

Key Points Anti-CD43– and anti-CD44–antibody coating immobilizes live mouse and human HSPCs. This enables 2D colony formation, medium exchange without cell-identification loss, and increased throughput of time-lapse imaging.

Site-specific antibody modification and immobilization on a microfluidic chip to promote the capture of circulating tumor cells and microemboli

Antibody coating via Fc-domain site-specific immobilization improves capture efficiency of circulating tumor cells and microemboli in microfluidics.

A Highly Sensitive Fluorescence Immunoassay for the Determination of Diethylstilbestrol

A highly sensitive direct competitive fluorescence immunoassay (FIA) was developed for the determination of diethylstilbestrol (DES), based on the antibody coating format using biotin-streptavidin amplification system. In the assay, DES competed with biotinylated goat anti-rabbit IgG for the immobilized antibody, then the streptavidin-FITC was added to link to the biotinylated goat anti-rabbit IgG as a tracer. Under optimal conditions, the assay provided a wide analytical range of 0.001-10000 ng/mL with a detection limit of 2.91×10-4ng/mL (R2=0.9943). This method was then applied to the determination of DES in chicken with satisfactory results

The use of an immunoelectron microscope-decoration technique to observe serological relationship of carlaviruses

An immunoelectron microscope-decoration technique was used to define serological relationships among carlaviruses (5 viruses and 9 antisera). The degree of relationship among these viruses was assessed on the basis of the intensity of antibody coating when the viruses were decorated with heterologous antibodies. A relationship was observed among PVM, PVS, CLV, CVB, LilMV, HoLV, HoMV and between WPSV and LilMV. PopMV was not related serologically to any of these viruses. The PVS particles were occasionally surrounded by an external spiral of an unidentified protein material.