Effect of prenatal administration of low dose antibiotics on gut microbiota and body fat composition of newborn mice

Yoshimoto, Ayumi; Uebanso, Takashi; Nakahashi, Mutsumi; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira

doi:10.3164/jcbn.17-53

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…The abundance of some taxa remained different over time, including higher abundance of bacteria in the Lachnospiraceae family, which has been associated with greater child weight [17], and lower abundance of Akkermansia muciniphila , a bacterium associated with metabolic health [18]. An experimental murine model [19] and an observational study in infants delivered preterm [20] also found that prenatal antibiotic exposure is associated with an altered infant microbiome composition. Other studies have found trimester-specific associations of antibiotics with fetal adipokines and birth weight [21], and observed that antibiotic exposure in the second trimester is associated with higher risk of childhood obesity [5–8].…”

Section: Discussionmentioning

confidence: 99%

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

Zhang

Differding

Benjamin‐Neelon

et al. 2019

Ann Clin Microbiol Antimicrob

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Background Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. Method In this prospective study (Nurture: recruitment 2013–2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. Results Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). Conclusions Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months. Electronic supplementary material The online version of this article (10.1186/s12941-019-0318-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

Zhang

Differding

Benjamin‐Neelon

et al. 2019

Ann Clin Microbiol Antimicrob

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“…All samples were prepared according to methods described by Human Metabolome Technologies, Inc. (HMT) (HMT, Tsuruoka, Japan) and in previous reports [24][25][26]. Briefly, the cecum luminal content, stool, cecum, liver, urine, and plasma were immediately frozen in liquid nitrogen and stored at −80 • C until metabolite extraction.…”

Section: Metabolome Analysis By Capillary Electrophoresis Electrospramentioning

confidence: 99%

Glycolate is a Novel Marker of Vitamin B2 Deficiency Involved in Gut Microbe Metabolism in Mice

et al. 2020

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Microbes in the human gut play a role in the production of bioactive compounds, including some vitamins. Although several studies attempted to identify definitive markers for certain vitamin deficiencies, the role of gut microbiota in these deficiencies is unclear. To investigate the role of gut microbiota in deficiencies of four vitamins, B2, B6, folate, and B12, we conducted a comprehensive analysis of metabolites in mice treated and untreated with antibiotics. We identified glycolate (GA) as a novel marker of vitamin B2 (VB2) deficiency, and show that gut microbiota sense dietary VB2 deficiency and accumulate GA in response. The plasma GA concentration responded to reduced VB2 supply from both the gut microbiota and the diet. These results suggest that GA is a novel marker that can be used to assess whether or not the net supply of VB2 from dietary sources and gut microbiota is sufficient. We also found that gut microbiota can provide short-term compensation for host VB2 deficiency when dietary VB2 is withheld.

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“…Evidence suggests that host–microbe interactions may extend beyond the local environment to peripheral tissues ( Marsland et al, 2015 ). Preclinical and human studies have demonstrated that maternal antibiotic administration during prenatal and intrapartum periods alters the bacterial composition and diversity of the offspring’s intestinal microbiota ( Gonzalez-Perez et al, 2016 ; Yoshimoto et al, 2018 ; Dierikx et al, 2020 ; Zimmermann and Curtis, 2020 ). Microbiota profiles play a crucial role in intestinal barrier function and intestinal maturation in germ-free mice and human infants ( Reinhardt et al, 2012 ; Sommer and Bäckhed, 2013 ; Kelly et al, 2015 ; Selma-Royo et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Maternal Antibiotic Treatment Disrupts the Intestinal Microbiota and Intestinal Development in Neonatal Mice

2021

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Maternal antibiotic treatment (MAT) during prenatal and intrapartum periods alters the bacterial composition and diversity of the intestinal microbiota of the offspring. The effect of MAT during pregnancy on the intestinal microbiota and its relationship with intestinal development remain unknown. This study investigated the effects of MAT during pregnancy on intestinal microbiota, injury and inflammation, vascularization, cellular proliferation, and the intestinal barrier in neonatal mice. At timed intervals, we fed pregnant C57BL/6N mice sterile drinking water containing antibiotics (ampicillin, gentamicin, and vancomycin; all 1 mg/ml) from gestational day 15 to delivery. The control dams were fed sterile drinking water. Antibiotic administration was halted immediately after birth. On postnatal day 7, the intestinal microbiota was sampled from the lower gastrointestinal tract and the ileum was harvested for histology, Western blot, and cytokines analyses. MAT significantly reduced the relative abundance of Bacteroidetes and Firmicutes and significantly increased the relative abundance of Proteobacteria in the intestine compared with their abundances in the control group. MAT also significantly increased intestinal injury score and cytokine levels, reduced the number of intestinal goblet cells and proliferating cell nuclear antigen-positive cells, and reduced the expressions of vascular endothelial growth factor and tight junction proteins. Therefore, we proposed that maternal antibiotic exposure during pregnancy disrupts the intestinal microbiota and intestinal development in neonatal mice.

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Effect of prenatal administration of low dose antibiotics on gut microbiota and body fat composition of newborn mice

Cited by 12 publications

References 25 publications

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

Glycolate is a Novel Marker of Vitamin B2 Deficiency Involved in Gut Microbe Metabolism in Mice

Maternal Antibiotic Treatment Disrupts the Intestinal Microbiota and Intestinal Development in Neonatal Mice

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