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

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.

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Testosterone disruptor effect and gut microbiome perturbation in mice: Early life exposure to doxycycline

Chemosphere ◽

10.1016/j.chemosphere.2019.01.101 ◽

2019 ◽

Vol 222 ◽

pp. 722-731 ◽

Cited By ~ 2

Author(s):

Xiang Hou ◽

Lei Zhu ◽

Xianwei Zhang ◽

Lili Zhang ◽

Hongduo Bao ◽

...

Keyword(s):

Gut Microbiome ◽

Early Life ◽

Early Life Exposure

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

10.1101/2020.03.11.987412 ◽

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

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Chemically Contaminated Eel Fed to Pregnant and Lactating Mouse Dams Causes Hyperactivity in Their Offspring

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000288 ◽

2016 ◽

Vol 86 (1-2) ◽

pp. 36-47 ◽

Cited By ~ 2

Author(s):

Imen Dridi ◽

Nidhal Soualeh ◽

Torsten Bohn ◽

Rachid Soulimani ◽

Jaouad Bouayed

Keyword(s):

Open Field ◽

Early Life ◽

Home Cage ◽

Anguilla Anguilla ◽

Acetylcholinesterase Activity ◽

Female Offspring ◽

Significant Inhibition ◽

Standard Diet ◽

Early Life Exposure ◽

Cage Test

Abstract.This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 – 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 – 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.

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Prenatal and Early-Life Exposure to Indoor Air-Polluting Factors and Allergic Sensitization at 2 Years of Age

PEDIATRICS ◽

10.1542/peds.2020-023861t ◽

2020 ◽

Vol 146 (Supplement 4) ◽

pp. S332.2-S333

Author(s):

Suzanne R. Kochis ◽

Jennifer Dantzer

Keyword(s):

Indoor Air ◽

Early Life ◽

Allergic Sensitization ◽

Early Life Exposure

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Early Life Exposure to Antibiotic Alters Energy Balance during Chronic High-Fat Feeding in Adult Male and Female Mice

Diabetes ◽

10.2337/db18-1999-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1999-P ◽

Cited By ~ 1

Author(s):

HYE LIM NOH ◽

SUJIN SUK ◽

RANDALL H. FRIEDLINE ◽

KUNIKAZU INASHIMA ◽

DUY A. TRAN ◽

...

Keyword(s):

Energy Balance ◽

Adult Male ◽

Early Life ◽

High Fat ◽

Male And Female ◽

Female Mice ◽

Early Life Exposure ◽

Fat Feeding

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Can a combination of vaccination, probiotic and organic acid treatment in layer hens protect against early life exposure to Salmonella Typhimurium and challenge at sexual maturity?

Vaccine ◽

10.1016/j.vaccine.2020.12.044 ◽

2020 ◽

Author(s):

Peter J. Groves ◽

Sarah L. Williamson ◽

Md. Ahaduzzaman ◽

Madeline Diamond ◽

Melanie Ngo ◽

...

Keyword(s):

Salmonella Typhimurium ◽

Organic Acid ◽

Early Life ◽

Acid Treatment ◽

Sexual Maturity ◽

Early Life Exposure ◽

Layer Hens

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Early Origins of Body Mass in Later Life: Examining Childhood Risks and Adult Pathways

Journal of Health and Social Behavior ◽

10.1177/00221465211005419 ◽

2021 ◽

pp. 002214652110054

Author(s):

Sarah A. Mustillo ◽

Miao Li ◽

Patricia Morton ◽

Kenneth F. Ferraro

Keyword(s):

Physical Activity ◽

Body Mass ◽

Health Risks ◽

Early Life ◽

Life Experiences ◽

Later Life ◽

Childhood Experiences ◽

Older Adulthood ◽

Early Life Exposure ◽

Nationally Representative

Prior research reveals that negative early-life experiences play a major role in the development of obesity in later life, but few studies identify mechanisms that alter the lifetime risk of obesity. This study examines the influence of negative childhood experiences on body mass index (BMI) and obesity (BMI ≥30) during older adulthood and the psychosocial and behavioral pathways involved. Using a nationally representative sample, we examine the influence of cumulative misfortune as well as five separate domains of misfortune on BMI and obesity. Results show that four of the five domains are associated with BMI and obesity either directly, indirectly, or both. The influence of cumulative misfortune on the outcomes is mediated by three adult factors: socioeconomic status, depressive symptoms, and physical activity. The mediators identified here provide targets for intervention among older adults to help offset the health risks of excess BMI attributable of early-life exposure to misfortune.

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