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Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.

ABSTRACT: Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequences of exposing neonate Wistar rats to an antibiotic-perturbed low-diversity microbiota from birth until weaning, without exposing the pups directly to antibiotics. Here, we show that pups born from both amoxicillin and vancomycin-treated dams gain less weight than controls. This was concordant with lower feed intake as well as increased colonic expression of the PYY satiety hormone gene at weaning. The weight difference persists into adulthood even though the initial differences in gut microbiota subsided. Our results demonstrate that early-life exposure to an antibiotic-perturbed low-diversity microbiota is sufficient to cause changes in body weight persisting into adulthood.

SUBMITTER: Tulstrup MV

PROVIDER: S-EPMC6137057 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.

Tulstrup Monica Vera-Lise MV Roager Henrik Munch HM Thaarup Ida Clement IC Frandsen Henrik Lauritz HL Frøkiær Hanne H Licht Tine Rask TR Bahl Martin Iain MI

Communications biology 20180913

Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequences of exposing neonate Wistar rats to an antibiotic-perturbed low-diversity microbiota from birth until weaning, without exposing the pups directly to ...[more]

PMID: 30272021

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Project description:Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children, yet specific therapies to treat TBI are lacking. Therapies that decrease the inflammatory response and enhance a reparative immune action may decrease oxidative damage and improve outcomes after TBI. Docosahexaenoic acid (DHA) modulates the immune response to injury in many organs. DHA given in the diet before injury decreased rat pup cognitive impairment, oxidative stress and white matter injury in our developmental TBI model using controlled cortical impact (CCI). Little is known about DHA effects on neuroinflammation in the developing brain. Further, it is not known if DHA given after developmental TBI exerts neuroprotective effects. We hypothesized that acute DHA treatment would decrease oxidative stress and improve cognitive outcome, associated with decreased pro-inflammatory activation of microglia, the brain's resident macrophages. METHODS:17-day-old rat pups received intraperitoneal DHA or vehicle after CCI or SHAM surgery followed by DHA diet or continuation of REG diet to create DHACCI, REGCCI, SHAMDHA and SHAMREG groups. We measured brain nitrates/nitrites (NOx) at post injury day (PID) 1 to assess oxidative stress. We tested memory using Novel Object Recognition (NOR) at PID14. At PID 3 and 7, we measured reactivity of microglial activation markers Iba1, CD68 and CD206 and astrocyte marker GFAP in the injured cortex. At PID3, 7 and 30 we measured mRNA levels of inflammation-related genes and transcription factors in flow-sorted brain cells. RESULTS:DHA decreased oxidative stress at PID1 and pro-inflammatory microglial activation at PID3. CCI increased mRNA levels of two interferon regulatory family transcription factors, blunted by DHA, particularly in microglia-enriched cell populations at PID7. CCI increased mRNA levels of genes associated with "pro- " and "anti-" inflammatory activity at PID3, 7 and 30. Most notably within the microglia-enriched population, DHA blunted increased mRNA levels of pro-inflammatory genes at PID 3 and 7 and of anti-inflammatory genes at PID 30. Particularly in microglia, we observed parallel activation of pro-inflammatory and anti-inflammatory genes. DHA improved performance on NOR at PID14 after CCI. CONCLUSIONS:DHA decreased oxidative stress and histologic and mRNA markers of microglial pro-inflammatory activation in rat pup brain acutely after CCI associated with improved short term cognitive function. DHA administration after CCI has neuroprotective effects, which may result in part from modulation of microglial activation toward a less inflammatory profile in the first week after CCI. Future and ongoing studies will focus on phagocytic function and reactive oxygen species production in microglia and macrophages to test functional effects of DHA on neuroinflammation in our model. Given its favorable safety profile in children, DHA is a promising candidate therapy for pediatric TBI.

Project description:Products containing BPA structural analog replacements have increased in response to growing public concern over adverse effects of BPA. Although humans are regularly exposed to a mixture of bisphenols, few studies have examined effects of prenatal exposure to BPA alternatives or bisphenol mixtures. In the present study, we investigate the effect of exposure to an environmentally-relevant, low-dose (150 ug/kg body weight per day) mixture of BPA, BPS, and BPF during gestation on the brain transcriptome in Long-Evans pups and dams using Tag RNA-sequencing. We also examined the association between dam licking and grooming, which also has enduring effects on pup neural development, and the transcriptomes. Associations between licking and grooming and the transcriptome were region-specific, with the hypothalamus having the greatest number of differentially expressed genes associated with licking and grooming in both dams and pups. Prenatal bisphenol exposure also had region-specific effects on gene expression and pup gene expression was affected more robustly than dam gene expression. In dams, the prelimbic cortex had the greatest number of differentially expressed genes associated with prenatal bisphenol exposure. Prenatal bisphenol exposure changed the expression of over 2000 genes in pups, with the majority being from the pup amygdala. We used Gene Set Enrichment Analysis (GSEA) to asses enrichment of gene ontology biological processes for each region. Top GSEA terms were diverse and varied by brain region and included processes known to have strong associations with steroid hormone regulation, cilium-related terms, metabolic/biosynthetic process terms, and immune terms. Finally, hypothesis-driven analysis of genes related to estrogen response, parental behavior, and epigenetic regulation of gene expression revealed region-specific expression associated with licking and grooming and bisphenol exposure that were distinct in dams and pups. These data highlight the effects of bisphenols on multiple physiological process that are highly dependent on timing of exposure (prenatal vs. adulthood) and brain region, and reiterate the contributions of multiple environmental and experiential factors in shaping the brain.

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Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.

Publications

Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.

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