Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments ...(PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.
The spread of antimicrobial resistance genes (ARGs) is a major public health crisis, with the ongoing spread of ARGs leading to reduced efficacy of antibiotic treatments. The gut microbiome is a key ...reservoir for ARGs, and because diet shapes the gut microbiome, diet also has the potential to shape the resistome. This diet-gut microbiome-resistome relationship may also be important in infants and young children. This narrative review examines what is known about the interaction between the infant gut microbiome, the infant resistome, and infant nutrition, including exploring the potential of diet to mitigate infant ARG carriage. While more research is needed, diet has the potential to reduce infant and toddler carriage of ARGs, an important goal as part of maintaining the efficacy of available antibiotics and preserving infant and toddler health.
In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity.
Our aim was to assess the association of early life innate immunity with the ...development of asthma in children at risk.
In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in
= 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the
gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years.
Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval CI, 1.13-3.16;
= 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40;
= 0.258,
= 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30;
= 0.002), which was in part mediated by the gut microbiome.
These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as ...autism spectrum disorder (ASD). Studies in rodent models have found long‐term neurobehavioral effects in offspring of ABx‐treated dams, but ASD‐relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD‐relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory‐guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx‐treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early‐life ABx exposure.
Abstract only
Secretory immunoglobulin A (sIgA) found in mother's milk reflects her immune response to a lifetime of infectious challenge and helps protect infants from many infectious diseases, ...including noroviruses (NVs). Some NV strains preferentially infect secretors (Se) ‐ individuals with a functional copy of the fucosyltransferase 2 (
FUT2
) gene, those lacking a functional copy are non‐secretors (Non‐Se). We tested the hypothesis that maternal secretor status alters the levels of strain‐specific NV antibodies in milk. We analyzed the relative levels of milk sIgA against two strains of NV ‐ strain 387, which preferentially infects Se, and strain 207 which does not preferentially infect Se individuals. Strain‐specific and total sIgA were analyzed using ELISA in week 4 milk samples from 79 mothers. Maternal
FUT2
genotype was analyzed by TaqMan assay to identify the 428G>A null mutation. The relationship between maternal secretor status and total, anti‐387, and anti‐207 sIgA was analyzed using Kruskal‐Wallis tests with Bonferroni correction. Non‐Se mothers had significantly lower levels of anti‐387 sIgA (p<0.001) in their milk. There were no significant differences in the amount of total or anti‐207 sIgA levels in milk based on maternal
FUT2
genotype. This study indicates that milk sIgA levels can be influenced by genetics as well as history of infection.
Grant Funding Source
: NICHD P01 HD 13021
Background: Small studies have found a connection between intestinal microbial colonization and risk of late-onset sepsis, but leave open questions about the generalizability of these findings. Also ...largely unstudied is the role of the host genotype in shaping the intestinal microbiome of the premature infant. Methods: The Novel Biomarkers Cohort is a large, prospective cohort of premature infants (born ≤32 weeks gestational age) enrolled from Neonatal Intensive Care Units (NICUs) in Birmingham, Alabama and Cincinnati, Ohio. Birmingham infants were compared Cincinnati infants to determine the degree to which findings regarding the microbiota may be generalizable between NICUs. Then, a nested case-control study of 66 infants was conducted to determine colonization patterns associated with late-onset sepsis. Finally, the microbiota of Cincinnati infants were analyzed to explore the contribution of host genetics to shaping the intestinal microbial community. Results: Of the NICUs, Birmingham preterm infants tend to have more stable bacterial communities during the first three weeks of life, with more Proteobacteria and Bacteriodes, and less Firmicutes than Cincinnati preterm infants. The composition of infant samples varied over calendar months and between postnatal weeks of life. Streptococcaceae and Clostridia were associated with sepsis in Birmingham and the Bacilli and the lack of Actinobacteria were associated with sepsis in Cincinnati. SNPs in specific fucosyltransferase and mucin genes were associated with higher or lower relative abundance of specific bacteria. However, these differences were not relevant to the patterns observed prior to sepsis.
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