scholarly journals Early-life microbial intervention reduces colitis risk promoted by antibiotic-induced gut dysbiosis

2020 ◽  
Author(s):  
Jun Miyoshi ◽  
Sawako Miyoshi ◽  
Tom O. Delmont ◽  
Candace Cham ◽  
Sonny T.M. Lee ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Gut Microbiome ◽  
Early Life ◽  
Experimental Colitis ◽  
List Type ◽  
Immune Disorder ◽  
Gut Dysbiosis ◽  
Early Life Exposure ◽  
Increased Risk ◽  
Bowel Diseases

SummaryPerturbations in the early life gut microbiome are associated with increased risk to complex immune disorder like inflammatory bowel diseases. We previously showed maternal antibiotic-induced gut dysbiosis vertically passed to offspring increases experimental colitis risk in IL-10 gene deficient (IL-10−/−) mice. While this could arise from emergence of pathobionts or loss/lack of essential microbes needed for appropriate immunological education, our findings suggest the latter. A dominant Bacteroides strain absent following antibiotic-induced perturbation was cultivated from murine fecal samples. Addition of this strain into mice with antibiotic-induced dysbiosis significantly promoted immune tolerance and reduced incidence of colitis in IL-10−/− mice, but only if engrafted early in life, and not during adulthood. Thus, key members of the gut microbiome are essential for development of immune tolerance to commensal microbes in early life and their addition in presence of gut dysbiosis during this period can reduce colitis risk in genetically prone hosts.HighlightsSpecific gut microbes promote early life immune tolerance to key commensal microbesLoss of early life keystone microbes increases colitis risk in genetically prone hostsEmergence of absent commensal microbes late in life worsened colitis outcomeEarly life exposure to a missing keystone Bacteroides strain reduced colitis risk

scholarly journals Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations

2020 ◽  
Vol 117 (44) ◽  
pp. 27549-27555
Author(s):  
Qu Cheng ◽  
Robert Trangucci ◽  
Kristin N. Nelson ◽  
Wenjiang Fu ◽  
Philip A. Collender ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Early Life ◽  
Food System ◽  
Cohort Analysis ◽  
Host Susceptibility ◽  
Sexually Transmitted ◽  
Global Food Security ◽  
Household Transmission ◽  
Early Life Exposure ◽  
Increased Risk

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958–1962)—the largest famine in human history—on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age–period–cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19–12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59–16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Neonatal exposure to BPA, BDE-99, and PCB produces persistent changes in hepatic transcriptome associated with gut dysbiosis in adult mouse livers

2021 ◽  
Author(s):  
Joe Jongpyo Lim ◽  
Moumita Dutta ◽  
Joseph L Dempsey ◽  
Hans-Joachim Lehmler ◽  
James MacDonald ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Gut Microbiome ◽  
Polybrominated Diphenyl Ethers ◽  
Early Life ◽  
Disease Risk ◽  
Neonatal Exposure ◽  
Environmental Toxicants ◽  
Early Life Exposure ◽  
Microbial Biomarkers ◽  
Hepatic Transcriptome

Abstract Recent evidence suggests that complex diseases can result from early life exposure to environmental toxicants. Polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and remain a continuing risk to human health despite being banned from production. Developmental BPA exposure mediated-adult onset of liver cancer via epigenetic reprogramming mechanisms has been identified. Here, we investigated whether the gut microbiome and liver can be persistently reprogrammed following neonatal exposure to POPs, and the associations between microbial biomarkers and disease-prone changes in the hepatic transcriptome in adulthood, compared to BPA. C57BL/6 male and female mouse pups were orally administered vehicle, BPA, BDE-99 (a breast milk-enriched PBDE congener), or the Fox River PCB mixture (PCBs), once daily for three consecutive days (postnatal days [PND] 2 to 4). Tissues were collected at PND5 and PND60. Among the three chemicals investigated, early life exposure to BDE-99 produced the most prominent developmental reprogramming of the gut-liver axis, including hepatic inflammatory and cancer-prone signatures. In adulthood, neonatal BDE-99 exposure resulted in a persistent increase in Akkermansia muciniphila throughout the intestine, accompanied by increased hepatic levels of acetate and succinate, the known products of A. muciniphila. In males, this was positively associated with permissive epigenetic marks H3K4me1 and H3K27, which were enriched in loci near liver cancer-related genes that were dysregulated following neonatal exposure to BDE-99. Our findings provide novel insights that early life exposure to POPs can have a life-long impact on disease risk, which may partly be regulated by the gut microbiome.

scholarly journals Early probiotic supplementation with B. infantis in breastfed infants leads to persistent colonization at 1 year

2021 ◽  
Author(s):  
Claire E. O’Brien ◽  
Anna K. Meier ◽  
Karina Cernioglo ◽  
Ryan D. Mitchell ◽  
Giorgio Casaburi ◽  
...  
Keyword(s):  
Breast Milk ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Bifidobacterium Longum ◽  
List Type ◽  
Probiotic Supplementation ◽  
Breastfed Infants ◽  
Follow Up Study ◽  
Increased Risk

Abstract Background Recent studies have reported a dysfunctional gut microbiome in breastfed infants. Probiotics have been used in an attempt to restore the gut microbiome; however, colonization has been transient, inconsistent among individuals, or has not positively impacted the host’s gut. Methods This is a 2-year follow-up study to a randomized controlled trial wherein 7-day-old infants received 1.8 × 1010 colony-forming unit Bifidobacterium longum subsp. infantis (B. infantis) EVC001 (EVC) daily for 21 days or breast milk alone (unsupplemented (UNS)). In the follow-up study, mothers (n = 48) collected infant stool at 4, 6, 8, 10, and 12 months postnatal and completed the health-diet questionnaires. Results Fecal B. infantis was 2.5–3.5 log units higher at 6–12 months in the EVC group compared with the UNS group (P < 0.01) and this relationship strengthened with the exclusion of infants who consumed infant formula and antibiotics. Infants in the EVC group had significantly higher Bifidobacteriaceae and lower Bacteroidaceae and Lachnospiraceae (P < 0.05). There were no differences in any health conditions between the two groups. Conclusions Probiotic supplementation with B. infantis within the first month postnatal, in combination with breast milk, resulted in stable colonization that persisted until at least 1 year postnatal. Impact A dysfunctional gut microbiome in breastfed infants is common in resource-rich nations and associated with an increased risk of immune diseases. Probiotics only transiently exist in the gut without persistent colonization or altering the gut microbiome. This is the first study to show that early probiotic supplementation with B. infantis with breast milk results in stable colonization of B. infantis and improvements to the gut microbiome 1 year postnatal. This study addresses a key gap in the literature whereby probiotics can restore the gut microbiome if biologically selected microorganisms are matched with their specific food in an open ecological niche.

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

2016 ◽  
Vol 2 (2) ◽  
Author(s):  
Antoine M. Snijders ◽  
Sasha A. Langley ◽  
Young-Mo Kim ◽  
Colin J. Brislawn ◽  
Cecilia Noecker ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Early Life ◽  
Host Genetics ◽  
Early Life Exposure

scholarly journals Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development

2019 ◽  
Vol 188 (8) ◽  
pp. 1503-1511 ◽  
Author(s):  
Shaina L Stacy ◽  
Jeanine M Buchanich ◽  
Zhen-qiang Ma ◽  
Christina Mair ◽  
Linda Robertson ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Early Life ◽  
Maternal Obesity ◽  
Birth Certificate ◽  
Cancer Development ◽  
Related Factors ◽  
Early Life Exposure ◽  
Increased Risk ◽  
Development Accounting ◽  
Newborn Size

Abstract Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother’s exposures before and during pregnancy could have important consequences for her child’s health, including cancer development. We examined whether birth certificate–derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth–related factors in childhood cancer development.

scholarly journals Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and promotes childhood atopy and asthma

2018 ◽  
Author(s):  
S.R. Levan ◽  
K.A. Stamnes ◽  
D.L. Lin ◽  
K.E. Fujimura ◽  
D.R. Ownby ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Immune Tolerance ◽  
Gut Microbiome ◽  
Early Life ◽  
Clinical Symptoms ◽  
Peroxisome Proliferator ◽  
Metagenomic Sequencing ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulated Gene Expression

AbstractNeonates at risk of childhood atopy and asthma are characterized by gut microbiome perturbation and fecal enrichment of 12,13 DiHOME(1); however, the underlying mechanism and source of this metabolite remain poorly understood. Here we show that 12,13 DiHOME treatment of human dendritic cells altered peroxisome proliferator-activated receptor γ regulated gene expression and decreased immune tolerance. In mice, 12,13 DiHOME treatment prior to airway challenge exacerbated pulmonary inflammation and decreased lung regulatory T cells. Neonatal fecal metagenomic sequencing revealed putative bacterial sources of 12,13 DiHOME. In our cohort, three bacterial genes and their product, 12,13 DiHOME, are associated with increased odds of childhood atopy or asthma, suggesting that early-life gut-microbiome risk factors may shape immune tolerance and identify high-risk neonates years in advance of clinical symptoms.One Sentence SummaryEarly-life gut-microbiome risk factors may shape immune tolerance and identify neonates at high-risk of disease.

scholarly journals Early-Life Exposure to Famine and Risk of MetabolicAssociated Fatty Liver Disease in Chinese Adults

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4063
Author(s):  
Jing Liu ◽  
Guimin Wang ◽  
Yiling Wu ◽  
Ying Guan ◽  
Zhen Luo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Early Life ◽  
Fatty Liver Disease ◽  
Chinese Adults ◽  
Early Life Exposure ◽  
Increased Risk ◽  
Famine Exposure

Background: Early-life exposure to the Chinese famine has been related to the risk of obesity, type 2 diabetes, and nonalcoholic fatty liver disease later in life. Nevertheless, the long-term impact of famine exposure on metabolic associated fatty liver disease (MAFLD), a recently proposed term to describe liver disease associated with known metabolic dysfunction, remains unknown. The aim of our study was to explore the relationship between early famine exposure and MAFLD in adulthood. Methods: A total of 26,821 participants (10,994 men, 15,827 women) were recruited from a cohort study of Chinese adults in Shanghai. We categorized participants into four famine exposure subgroups based on the birth year as nonexposed (1963–1967), fetal-exposed (1959–1962), childhood-exposed (1949–1958), and adolescence-exposed (1941–1948). MAFLD was defined as liver steatosis detected by ultrasound plus one of the following three criteria: overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. Multivariable logistic regression models were performed to examine the association between famine exposure and MAFLD. Results: The mean ± standard deviation age of the participants was 60.8 ± 6.8 years. The age-adjusted prevalence of MAFLD was 38.3, 40.8, 40.1, and 36.5% for the nonexposed, fetal-exposed, childhood-exposed, and adolescence-exposed subgroups, respectively. Compared with nonexposed participants, fetal-exposed participants showed an increased risk of adulthood MAFLD (OR = 1.10, 95% CI 1.00–1.21). The significant association between fetal famine exposure and MAFLD was observed in women (OR = 1.22, 95% CI 1.08–1.37), but not in men (OR = 0.88, 95% CI 0.75–1.03). In age-balanced analyses combining pre-famine and post-famine births as the reference, women exposed to famine in the fetal stage still had an increased risk of MAFLD (OR = 1.15, 95% CI 1.05–1.26). Conclusions: Prenatal exposure to famine showed a sex-specific association with the risk of MAFLD in adulthood.

scholarly journals Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030427 ◽  
Author(s):  
Wei Perng ◽  
Marcela Tamayo-Ortiz ◽  
Lu Tang ◽  
Brisa N Sánchez ◽  
Alejandra Cantoral ◽  
...  
Keyword(s):  
Lead Exposure ◽  
Early Life ◽  
Calcium Supplementation ◽  
Dietary Factors ◽  
Environmental Toxicants ◽  
Neurocognitive Deficits ◽  
Early Life Exposure ◽  
Increased Risk ◽  
Maternity Hospitals ◽  
Pregnancy And Lactation

PurposeThe Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother–child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes.Participantsn=1643 mother–child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico.Findings to dateMaternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.Future plansAs the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.Trial registration numberNCT00558623.

scholarly journals Early-life exposure to the Chinese famine of 1959–61 and risk of Hyperuricemia: results from the China health and retirement longitudinal study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenqiang Zhang ◽  
Rongsheng Luan
Keyword(s):  
Early Childhood ◽  
Uric Acid ◽  
Longitudinal Study ◽  
Serum Uric Acid ◽  
Early Life ◽  
Early Life Exposure ◽  
Long Term Effect ◽  
Increased Risk ◽  
Famine Exposure

Abstract Background Short-term starvation has been related to hyperuricemia. However, little is known about the long-term effect of early-life exposure to famine on hyperuricemia risk in adulthood. Methods The analysis included 2383 participants from the China Health and Retirement Longitudinal Study in 2015. Hyperuricemia was diagnosed as serum uric acid ≥7 mg/dL in men and serum uric acid ≥6 mg/dL in women. Famine exposure subgroups were defined as unexposed (born between October 1, 1962, and September 30, 1964), fetal-exposed (born between October 1, 1959, and September 30, 1961), and early-childhood exposed (born between October 1, 1956, and September 1, 1958). The association between early-life famine exposure and hyperuricemia risk was assessed using multivariate logistic regression. Results The prevalence of hyperuricemia in the unexposed, fetal-exposed, and early-childhood exposed participants was 10.7, 14.1, 11.1%, respectively. Compared with unexposed and early-childhood exposed participants combined as an age-balanced control, fetal-exposed participants showed an increased risk of hyperuricemia in adulthood (OR = 1.41; 95% CI: 1.06–1.88), after adjusting for gender, marital status, famine severity, residence, smoking, drinking, BMI, hypertension, and diabetes. The famine effect on hyperuricemia was accentuated by overweight or obesity (P for interaction = 0.042). Compared with unexposed and BMI < 24 kg/m2 participants, the OR (95%CI) of hyperuricemia was 3.66 (2.13–6.30) for fetal-exposed and overweight/obesity participants. However, combined unexposed and early-childhood exposed participants as an age-balanced control, the interaction of famine exposure and BMI was not statistically significant (P for interaction = 0.054). Conclusion Famine exposure in the fetal stage was associated with an increased risk of hyperuricemia in adulthood.

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