Infant Gut Microbiome Research Articles

Association of the Infant Gut Microbiome with Temperament at Nine Months of Age: A Michigan Cohort Study.

Though studies in animals and humans link the gut microbiota to brain development and control of behavior, little research has examined this connection in healthy infants. This prospective study could determine associations between infant gut microbiota at 3 months, and infant temperament at 9 months, in a prospective pregnancy cohort (Michigan Archive for Research on Child Health; n = 159). Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at 3 months of age. Based on the relative abundance of gut microbiotas, three groups were identified, and each group was characterized by different microbes. Infant temperament outcomes were reported by mothers using the Infant Behavior Questionnaire-Revised Very Short Form at a mean age of 9.4 months. Fully adjusted multivariate linear regression models showed that certain clusters were associated with higher negative emotionality scores, prominently among infants who had poor vitamin D intake. However, no associations were evident between gut microbiota clusters and temperament scales after FDR correction. After using three differential abundance tools, Firmicutes was associated with higher positive affect/surgency scores, whereas Clostridioides was associated with lower scores. An association between the gut microbiota and early infancy temperament was observed; thus, this study warrants replication, with a particular focus on vitamin D moderation.

Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species. Finally, we compared the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance of unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.

CRISPR-Cas-based identification of a sialylated human milk oligosaccharides utilization cluster in the infant gut commensal Bacteroides dorei

The infant gut microbiome is impacted by early-life feeding, as human milk oligosaccharides (HMOs) found in breastmilk cannot be digested by infants and serve as nutrients for their gut bacteria. While the vast majority of HMO-utilization research has focused on Bifidobacterium species, recent studies have suggested additional HMO-utilizers, mostly Bacteroides, yet their utilization mechanism is poorly characterized. Here, we investigate Bacteroides dorei isolates from breastfed-infants and identify that polysaccharide utilization locus (PUL) 33 enables B. dorei to utilize sialylated HMOs. We perform transcriptional profiling and identity upregulated genes when growing on sialylated HMOs. Using CRISPR-Cas12 to knock-out four PUL33 genes, combined with complementation assays, we identify GH33 as the critical gene in PUL33 for sialylated HMO-utilization. This demonstration of an HMO-utilization system by Bacteroides species isolated from infants opens the way to further characterization of additional such systems, to better understand HMO-utilization in the infant gut.

Impact of complementary feeding on infant gut microbiome, metabolites and early development.

Introducing complementary foods is critical for promoting infant health and development. During the weaning period, the dietary patterns provide essential nutrients and facilitate the development of a diverse gut microbiome, which plays significant roles in the regulation of immune, metabolic, and neurological functions. This study enrolled 200 families to assess the impact of complementary feeding on infant growth and health outcomes. Data included detailed records of feeding practices, infant growth measurements, health assessments, and fecal samples and breast milk collected between weeks 12 and 32 postpartum. The gut microbiome was analyzed using 16S rRNA sequencing, while metabolites such as human milk oligosaccharides (HMOs), monosaccharides, and short-chain fatty acids (SCFAs) were measured using chromatography-mass spectrometry. Results revealed a high prevalence of breastfeeding, with complementary food introduced at around 16 weeks. Significant alterations in the infant gut microbiome were observed, particularly in the genera Lactobacillus, Akkermansia, and Staphylococcus. Additionally, the levels of HMOs, monosaccharides, and SCFAs were found to be influenced by the introduction of complementary foods. Significant correlations emerged between complementary feeding practices, gut microbiome diversity, specific bacterial genera (e.g., Streptococcus, Lactobacillus, Bifidobacterium, and Clostridioides), and key metabolites (such as lacto-N-tetraose, lacto-N-neotetraose, mannose, and butyric acid). This study offers valuable insights into the complex interactions between complementary feeding, gut microbiome development, and metabolite profiles during early infant growth. Future research with larger cohorts and targeted dietary interventions is recommended to further elucidate the underlying mechanisms.

Screening competition and cross-feeding interactions during utilization of human milk oligosaccharides by gut microbes.

Background: The infant gut microbiome is a complex community that influences short- and long-term health. Its assembly and composition are governed by variables such as the feeding type. Breast milk provides infants an important supply of human milk oligosaccharides (HMO), a broad family of carbohydrates comprising neutral, fucosylated, and sialylated molecules. There is a positive association between HMOs and the overrepresentation of Bifidobacterium species in the infant gut, which is sustained by multiple molecular determinants present in the genomes of these species. Infant-gut-associated Bifidobacterium species usually share a similar niche and display similar HMO inclinations, suggesting they compete for these resources. There is also strong evidence of cross-feeding interactions between HMO-derived molecules and bifidobacteria. Methods: In this study, we screened for unidirectional and bidirectional interactions between Bifidobacterium and other species using individual HMO. Bifidobacterium bifidum and Bacteroides thetaiotaomicron increased the growth of several other species when their supernatants were used, probably mediated by the partial degradation of HMO. In contrast, Bifidobacterium longum subsp. infantis. supernatants did not exhibit positive growth. Results: Bifidobacterium species compete for lacto-N-tetraose, which is associated with reduced bidirectional growth. The outcome of these interactions was HMO-dependent, in which the two species could compete for one substrate but cross-feed on another. 2'-fucosyllactose and lacto-N-neotetraose are associated with several positive interactions that generally originate from the partial degradation of these HMOs. Conclusion: This study presents evidence for complex interactions during HMO utilization, which can be cooperative or competitive, depending on the nature of the HMO. This information could be useful for understanding how breast milk supports the growth of some Bifidobacterium species, shaping the ecology of this important microbial community.

Delivery mode and maternal gestational diabetes are important factors in shaping the neonatal initial gut microbiota.

The infant gut microbiome's establishment is pivotal for health and immune development. Understanding it unveils insights into growth, development, and maternal microbial interactions. Research often emphasizes gut bacteria, neglecting the phageome. To investigate the influence of geographic or maternal factors (mode of delivery, mode of breastfeeding, gestational diabetes mellitus) on the gut microbiota and phages of newborns, we collected fecal samples from 34 pairs of mothers and their infants within 24 hours of delivery from three regions (9 pairs from Enshi, 7 pairs from Hohhot, and 18 pairs from Hulunbuir) using sterile containers. Gut microbiota analysis by Shotgun sequencing was subsequently performed. Our results showed that geographic location affects maternal gut microbiology (P < 0.05), while the effect on infant gut microbiology was not significant (P = 0.184). Among the maternal factors, mode of delivery had a significant (P < 0.05) effect on the newborn. Specific bacteria (e.g., Bacteroides, Escherichia spp., Phocaeicola vulgatus, Escherichia coli, Staphylococcus hominis, Veillonella spp.), predicted active metabolites, and bacteriophage vOTUs varied with delivery mode. Phocaeicola vulgatus significantly correlated with some metabolites and bacteriophages in the early infant gut (P < 0.05). In the GD group, a strong negative correlation of phage diversity between mother and infants was observed (R = -0.58, P=0.04). In conclusion, neonatal early gut microbiome (including bacteria and bacteriophages) colonization is profoundly affected by the mode of delivery, and maternal gestational diabetes mellitus. The key bacteria may interact with bacteriophages to influence the levels of specific metabolites. Our study provides new evidence for the study of the infant microbiome, fills a gap in the analysis of the infant gut microbiota regarding the virome, and emphasizes the importance of maternal health for the infant initial gut virome.

Literature Review: Infant formulas with human milk oligosaccharides on gut microbiome and intestinal immune system

Background: Infant formula has a similar composition to breast milk, especially on key components like proteins, fats, and functional oligosaccharides. However, significant differences exist between bovine milk-based formula and human breast milk, particularly in the abundance and diversity of human milk oligosaccharides (HMOs). HMOs are pivotal in shaping the infant gut microbiome and immune system, with potential implications for infant health and development.Objectives: The literature review aimed to explore the role of HMOs in shaping the gut microbiome and strengthening the intestinal immune system in infants.Methods: Descriptive research was carried out in May-August 2023 using the literature review method. The design and implementation of this study referred to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for Randomized Controlled Trials (RCTs). Literature sources were obtained from PubMed, Elsevier, Medline, Nature, PLOS, MPDI, JAMA, and Scopus publication databases with a limitation of the last ten years (2013-2023). One hundred twenty articles were obtained with these keywords and then selected in stages according to predetermined criteria. Six articles that met the criteria were retrieved from 2013-2023. The articles obtained were compiled, analyzed, and concluded by looking for similarities and dissimilarities, giving views, comparing, and summarizing.Results: The review revealed that HMOs significantly influenced the composition and function of the infant's intestinal microbiota, inhibiting harmful pathogens in the intestine. Therefore, HMOs as prebiotics were crucial in promoting intestinal immune system health in infants.Conclusion: Human Milk Oligosaccharides (HMOs) in infant formula substantially impacted the gut microbiome composition and the infant's intestinal immune system. Studies consistently showed that HMOs influenced the growth and diversity of gut bacteria, leading to outcomes similar to those seen in breastfed infants.

Prebiotics increase iron absorption and reduce the adverse effects of iron on the gut microbiome and inflammation: a randomized controlled trial using iron stable isotopes in Kenyan infants

BackgroundIron fortificants tend to be poorly absorbed and may adversely affect the gut, especially in African children. ObjectiveWe assessed the effects of prebiotic galacto-oligosaccharides/fructo-oligosaccharides (GOS/FOS) on iron absorption and gut health when added to iron-fortified infant cereal. MethodsWe randomly assigned Kenyan infants (n = 191) to receive daily for 3 wk a cereal containing iron and 7.5 g GOS/FOS (7.5 g+iron group), 3 g (3-g+iron group) GOS/FOS, or no prebiotics (iron group). A subset of infants in the 2 prebiotic+iron groups (n = 66) consumed 4 stable iron isotope–labeled test meals without and with prebiotics, both before and after the intervention. Primary outcome was fractional iron absorption (FIA) from the cereal with or without prebiotics regardless of dose, before and after 3 wk of consumption. Secondary outcomes included fecal gut microbiota, iron and inflammation status, and effects of prebiotic dose. ResultsMedian (25th–75th percentiles) FIAs from meals before intervention were as follows: 16.3% (8.0%–27.6%) without prebiotics compared with 20.5% (10.4%–33.4%) with prebiotics (Cohen d = 0.53; P < 0.001). FIA from the meal consumed without prebiotics after intervention was 22.9% (8.5%–32.4%), 41% higher than from the meal without prebiotics before intervention (Cohen d = 0.36; P = 0.002). FIA from the meal consumed with prebiotics after intervention was 26.0% (12.2%–36.1%), 60% higher than from the meal without prebiotics before intervention (Cohen d = 0.45; P = 0.007). After 3 wk, compared with the iron group, the following results were observed: 1) Lactobacillus sp. abundances were higher in both prebiotic+iron groups (P < 0.05); 2) Enterobacteriaceae sp. abundances (P = 0.022) and the sum of pathogens (P < 0.001) were lower in the 7.5-g+iron group; 3) the abundance of bacterial toxin-encoding genes was lower in the 3-g+iron group (false discovery rate < 0.05); 4) fecal pH (P < 0.001) and calprotectin (P = 0.033) were lower in the 7.5-g+iron group. ConclusionsAdding prebiotics to iron-fortified infant cereal increases iron absorption and reduces the adverse effects of iron on the gut microbiome and inflammation in Kenyan infants.This trial was registered at clinicaltrials.gov as NCT03894358.

Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial

ABSTRACT The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.

Gut microbiota transfer evidence from mother to newborn.

Early life microbiota is a risk factor for future diseases. The main purpose of this study was to investigate the transfer of gut microbiota from mother to newborn. A biological sample was collected from the anal mucosa of the pregnant women before delivery and from the newborns between 24 and 48h after delivery, as it was not possible to collect a meconium sample at that time. The microbiome of the samples was analyzed by sequencing the hypervariable regions V3-V4 of the 16S gene. To determine the likelihood of microbiota transfer from mother to newborn and examine the relationship with the mode of delivery, we utilized Fisher's exact test and odds ratio. A weighted transfer ratio was employed as a comprehensive measure of transfer. A total of 5767 ASVs were identified in newborn samples (n = 30) and 7253 in maternal samples (n = 30). In the analysis of transfer correlated with the mode of delivery, we observed significant ASVs (p < 0.05). Vaginal delivery showed a positive probability of transfer (OR = 2.184 and WTR = 1.852). We found a negative correlation (OR < 1) between the abundance of maternal ASVs and the likelihood of microbiota transfer to the newborn in both delivery modes. The relationship was inversely proportional for both cesarean section (log10 = - 0.2229) and vaginal delivery (log10 = - 0.1083), with statistical significance observed only for cesarean section (p = 0.0083). Conclusion:In our sample, the maternal gut microbiome was found to be associated with the infant gut microbiome, indicating evidence of ASV-specific transfer from the maternal microbiome to newborns. What is Known: • There is a relationship of early-life microbiota composition with future health outcomes. What is New: • This was the first study to evaluate maternal gut microbiota transfer to newborns in Brazil.

276 Investigating the Colonization History of Early-Life Microbiome of Piglets

Abstract Early-life microbiome establishment and colonization is essential for gut development, nutrient digestion and metabolism, and modulation of the immune system. Microbial colonization of the infant digestive tract begins at birth, and as such, maternal microbiota has an important influence on the early-life establishment and colonization of the infant gut microbiota. Therefore, perturbations during early life establishment of the infant gut microbiome may have long-term impact on the microbiota composition and function, and may serve as a major determinant on host health and development. To evaluate the effects of early life microbiomes on long-term colonization of the microbiome, and effect host function, we set out to quantify the percentage of the sow microbiome that contributes to early-life colonization in the piglet and how such microbiomes would persist within the piglet gut. To this end, we investigated the colonization history and the role of the sow microbiome in establishment of the piglet microbiome over time using 16S rRNA sequencing. We observed 125 amplicon sequence variants to be persistent across different sampling time points, day 0, day 14, and day 21, representing 89.73%, 68.99%, and 67.30% of the total reads on day 0, day 14 and day 21, recovered from the piglets respectively. Comparing the piglet microbiota to that of the sow, we observed 114 of the 125 persistent ASVs in the piglet microbiota to arise from the sow that account for 75% of the total reads in the sow microbiota. This core microbiome includes Bacteroides, Methanobrevibacter, Lachnoclostridium, Lactobacillus, Escherichia-Shigella, Clostridium sensu stricto 1, Christensenellaceae R-7 group, Ruminococcaceae Genus, Romboutsia, Phascolarctobacterium, Erysipelotrichaceae Genus, Muribaculaceae Genus, Streptococcus, [Eubacterium] coprostanoligenes group Genus and others. The species abundance increased for Bacteroides, Methanobrevibacter, Lachnoclostridium, Clostridium sensu stricto 1, Lactobacillus, Christensenellaceae R-7 group, Ruminococcaceae Genus, Romboutsia, Phascolarctobacterium, Erysipelotrichaceae Genus, Muribaculaceae Genus, Streptococcus, [Eubacterium] coprostanoligenes group Genus and other species over time while species abundance of pathogens or opportunistic pathogens such as Escherichia-Shigella and Salmonella species decreased over time. In conclusion, the maternal microbiota has an important role in early-life microbiome establishment and can be utilized to develop a more beneficial microbiome to increase pig health and productivity.

Oral lactoferrin administration does not impact the diversity or composition of the infant gut microbiota in a Peruvian cohort.

Lactoferrin is a protein from breast milk involved in early-life microbiome assembly. It is believed to promote the growth of lactic acid-producing bacteria and inhibit pathogens by limiting iron availability and enabling an acidic environment in the gut. Previous reports suggest that oral administration of lactoferrin in neonates promotes the increase of gut microbiota diversity and the enrichment of beneficial microbes. However, its effect on infant gut microbiota over time has yet to be thoroughly studied to fully understand its potential as a prebiotic. Using 16s rRNA gene amplicon sequencing, we analyzed the gut microbiota composition of 60 toddlers at 12-18 months of age from Lima, Peru, who received daily oral administration of lactoferrin or placebo for 6 months since enrollment. Samples were analyzed at 0, 2, and 4 months after beginning treatment. Our results show that lactoferrin treatment does not increase gut microbiota diversity over time nor affect its bacterial composition compared to the placebo group.IMPORTANCEPrevious studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.

Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.

There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.

Maternal vitamin D in pregnancy and infant's gut microbiota: a systematic review.

An infant's gut microbiome plays a vital role in their health, and various factors can impact their gut microbiota composition. This review aimed to summarize the current knowledge regarding the associations between maternal prenatal supplementation with vitamin D and the composition of infants' gut microbiota. A comprehensive systematic search was done on Web of Science, Scopus, PubMed, ScienceDirect, and Google Scholar databases without date restrictions until December 2022 using relevant keywords. All relevant original articles in English were eligible for the present review. Eight articles (two mice, three randomized clinical trials, and three cohort studies) were included in this review. The included mice studies reported that maternal prenatal vitamin D supplementation significantly affects the offspring's gut microbiome composition (such as enhancing the abundance of colonic Bacteroides). Moreover, the included cohort studies revealed a significant association between maternal supplementation with vitamin D during pregnancy and the infant's gut microbiome. However, one-third of clinical trials indicated that vitamin D levels in utero could influence the colonization of the microbial community in the infant's gut. The findings of this review revealed that maternal vitamin D supplementation during pregnancy was linked to an infant's gut microbiome and could impact their gut microbiota composition. However, more studies are warranted to confirm these results.

Parity modulates impact of BMI and gestational weight gain on gut microbiota in human pregnancy

ABSTRACT Dysregulation of maternal adaptations to pregnancy due to high pre-pregnancy BMI (pBMI) or excess gestational weight gain (GWG) is associated with worsened health outcomes for mothers and children. Whether the gut microbiome contributes to these adaptations is unclear. We longitudinally investigated the impact of pBMI and GWG on the pregnant gut microbiome. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed on to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role of the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants. Understanding how these factors contribute to and shape maternal health is essential for the development of interventions impacting the microbiome, including pre/probiotics.

SAT052 Prolonged Nursing Augments Short Chain Fatty Acid Levels And Leads To Amelioration Of Type 1 Diabetes

Abstract Disclosure: S. rafiqi: None. Z. Zahid: None. R. Lamendella: None. O. aghogho: None. E. Gionfriddo: None. Y. Tao: None. J.C. Jaume: None. S. Imam: None. The infant gut microbiome essentially shifts to a diverse and complex microbial system during weaning on separation from the mother and any perturbations lead to pathological imprinting with lifelong implications. Apart from breast milk, the microbiota of the skin and the intimate niche between mother and offspring contribute to gut microbial composition. Gut microbiome dysbiosis has been ascribed in the initiation and/or perpetuation of type 1 diabetes (T1D) in human and animal models. The gut microbial diversification is manifested as change in microbial metabolites particularly short-chain fatty acids (SCFAs) that have direct and indirect roles in immune regulation and epithelial barrier integrity. In this study, we try to decipher the role of prolonged nursing of newborn mice (upto 45 days) in the amelioration of type 1 diabetes in the context of changes in the gut microbiome and microbial metabolites. The humanized T1D mice used in the study spontaneously develop T1D at 3-4 weeks of age and are normally weaned at 21 days. Our results revealed mice subjected to prolonged nursing had consistent increments in levels of butyric acid from 60 to 150 days of age as compared to normal weaned mice, owing to a stable population of SCFA-producing bacteria developed during prolonged nursing with the mother. The normal weaned mice had a transient increase of butyric acid at 60 days but it didn’t sustain till the 150th day. The steady levels of butyrate in prolonged nursed mice exerted immunoregulatory roles which manifested in the enrichment of regulatory T cells (Tregs) in the intestinal mesenteric epithelium, payer’s patches, peri pancreatic lymph nodes (PLN), pancreas (PN) and spleen. The enrichment of Tregs leads to the regulation of diabetogenic Th1, Th17, and interferon gamma-producing CD8 T cells (cytotoxic lymphocytes, CTLs) at PLN, PN, and spleen. This increased immune tolerance was mirrored by improved glucose homeostasis and fasting blood glucose levels in the prolonged nursing group. Prolonged nursing preserved the pancreatic islet architecture and significantly maintained the increased number of islets per pancreas as observed in H&amp;E sections. Also, it could be inferred from the results that SCFA’s promoted intestinal integrity with increased submucosal thickening, longer villi, and shallower crypts in the intestine of prolonged nursed mice. In conclusion, prolonged nursing accounts for gradual and steady gut microbiota succession in infants that augments SCFA production leading to enrichment of T regulatory cells and less aggressive diabetes. Presentation: Saturday, June 17, 2023

Randomised controlled trial of exercise training during lactation on breast milk composition in breastfeeding people with overweight/obesity: a study protocol for the MILKSHAKE trial

Breast milk from people with overweight/obesity may differ in composition compared with that from normal-weight people. Exercise training can modify breast milk composition in rodent models, with a beneficial impact...

Infants exposed in utero to Hurricane Maria have gut microbiomes with reduced diversity and altered metabolic capacity.

The gut microbiome is a potentially important mechanism that links prenatal disaster exposures with increased disease risks. However, whether prenatal disaster exposures are associated with alterations in the infant's gut microbiome remains unknown. We established a birth cohort study named Hurricane as the Origin of Later Alterations in Microbiome (HOLA) after Hurricane Maria struck Puerto Rico in 2017. We enrolled vaginally born Latino term infants aged 2 to 6 months, including n = 29 infants who were exposed in utero to Hurricane Maria in Puerto Rico and n = 34 infants who were conceived at least 5 months after the hurricane as controls. Shotgun metagenomic sequencing was performed on infant stool swabs. Infants exposed in utero to Hurricane Maria had a reduced diversity in their gut microbiome compared to the control infants, which was mainly seen in the exclusively formula-fed group (P = 0.02). Four bacterial species, including Bacteroides vulgatus, Clostridium innocuum, Bifidobacterium pseudocatenulatum, and Clostridium neonatale, were depleted in the exposure group compared to the control group. Compositional differences in the microbial community and metabolic genes between the exposure and control groups were significant, which were driven by the formula feeding group (P = 0.02 for the microbial community and P = 0.008 for the metabolic genes). Metabolic modules involved in carbohydrate metabolism were reduced in the exposure group. Prenatal maternal exposure to Hurricane Maria was associated with a reduced gut commensal and an altered microbial composition and metabolic potential in the offspring's gut. Breastfeeding can adjust the composition of the gut microbiomes of exposed infants. IMPORTANCE Climate change is a serious issue that is affecting human health. With more frequent and intense weather disasters due to climate change, there is an urgent need to evaluate and understand the impacts of prenatal disaster exposures on the offspring. The prenatal stage is a particularly vulnerable stage for disease origination. However, the impact of prenatal weather disaster exposures on the offspring's gut microbiome has not been evaluated. Our HOLA study starts to fill this knowledge gap and provides novel insights into the microbiome as a mechanism that links prenatal disaster exposures with elevated disease risks. Our major finding that reduced microbial diversity and altered metabolic capacity are associated with prenatal hurricane exposures warrants further studies to evaluate the impact of weather disasters on the unborn.

Social and psychological adversity are associated with distinct mother and infant gut microbiome variations

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in the mothers and children indicate that different discriminatory taxa and related pathways are involved, including many species of Bifidobacterium and related pathways across several comparisons. The lowest inter-individual gut microbiome similarity was observed among high-social disadvantage/high-psychosocial stressors mothers, suggesting distinct environmental exposures driving a diverging gut microbiome assembly compared to low-social disadvantage/low-psychosocial stressors controls (P = 3.5 × 10−5 for social disadvantage, P = 2.7 × 10−15 for psychosocial stressors). Children’s gut metagenome profiles at 4 months also significantly predicted high/low maternal prenatal IL-6 (P = 0.029), with many bacterial species overlapping those identified by social disadvantage and psychosocial stressors. These differences, based on maternal social and psychological status during a critical developmental window early in life, offer potentially modifiable targets to mitigate health inequities.

Associations between Dietary Sugar and Fiber with Infant Gut Microbiome Colonization at 6 Mo of Age

BackgroundThe taxonomic composition of the gut microbiome undergoes rapid development during the first 2–3 y of life. Poor diet during complementary feeding has been associated with alterations in infant growth and compromised bone, immune system, and neurodevelopment, but how it may affect gut microbial composition is unknown. ObjectivesThis cross-sectional study aimed to examine the associations between early-life nutrition and the developing infant gut microbiota at 6 mo of age. MethodsLatino mother–infant pairs from the Mother’s Milk Study (n = 105) were included. Infant gut microbiota and dietary intake were analyzed at 6 mo of age using 16S ribosomal RNA amplicon sequencing and 24-h dietary recalls, respectively. Poisson generalized linear regression analysis was performed to examine associations between dietary nutrients and microbial community abundance while adjusting for infants’ mode of delivery, antibiotics, infant feeding type, time of introduction of solid foods, energy intake, and body weight. A P value of <0.05 was used to determine the statistical significance in the study. ResultsInfants with higher consumption of total sugar exhibited a lower relative abundance of the genera Bacteroides (β = −0.01; 95% CI: −0.02, −0.00; P = 0.03) and genus Clostridium belonging to the Lachnospiraceae family (β = −0.02; 95% CI: −0.03, −0.00; P = 0.01). In addition, a higher intake of free sugar (which excludes sugar from milk, dairy, and whole fruit) was associated with several bacteria at the genus level, including Parabacteroides genus (β = 0.03; 95% CI: 0.01, 0.05; P = 0.001). Total insoluble fiber intake was associated with favorable bacteria at the genus level such as Faecalibacterium (β = 0.28; 95% CI: 0.03, 0.52; P = 0.02) and Coprococcus (β = 0.28; 95% CI: 0.02, 0.52; P = 0.03). ConclusionThese findings demonstrate that early-life dietary intake at 6 mo impacts the developing gut microbiome associated with the presence of both unfavorable gut microbes and dietary fiber-associated commensal microbes.