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Long-term dysbiosis and fluctuations of gut microbiome in antibiotic treated preterm infants.

ABSTRACT: Postnatal acquisition of the microbiome is critical to infant health. In preterm infants, empiric use of antibiotics is common, with significant health consequences. To understand the influence of antibiotics on acquisition of the microbiome over time, we longitudinally profiled microbial 16S rRNA in the stool of 79 preterm infants during their hospitalization in the intensive care unit and compared antibiotic treated and untreated infants. Despite similar clinical presentation, antibiotic treated infants had strong deviations in the content, diversity, and most dramatically, temporal stability of their microbiome. Dysbiosis and fluctuations of microbiome content persisted long after antibiotic exposure, up to hospital discharge. Microbiome diversity was dominated by a few common bacteria consistent among all infants. Our findings may inform clinical practice related to antibiotic use and targeted microbial interventions aimed at overcoming the adverse influence of antibiotics on the microbiome of preterm infants at specific developmental time points.

SUBMITTER: Cetinbas M

PROVIDER: S-EPMC10565780 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Long-term dysbiosis and fluctuations of gut microbiome in antibiotic treated preterm infants.

Cetinbas Murat M Thai Julie J Filatava Evgenia E Gregory Katherine E KE Sadreyev Ruslan I RI

iScience 20230922 10

Postnatal acquisition of the microbiome is critical to infant health. In preterm infants, empiric use of antibiotics is common, with significant health consequences. To understand the influence of antibiotics on acquisition of the microbiome over time, we longitudinally profiled microbial 16S rRNA in the stool of 79 preterm infants during their hospitalization in the intensive care unit and compared antibiotic treated and untreated infants. Despite similar clinical presentation, antibiotic treat ...[more]

PMID: 37829203

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Project description:BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants.

Project description:Tributyrin (TB) is a butyric acid precursor and has a key role in anti-inflammatory and intestinal barrier repair effects by slowly releasing butyric acid. However, its roles in gut microbiota disorder caused by antibiotics remain unclear. Herein, we established an intestinal microbiota disorder model using ceftriaxone sodium via gavage to investigate the effects of different TB doses for restoring gut microbiota and intestinal injury. First, we divided C57BL/6 male mice into two groups: control (NC, n = 8) and experimental (ABx, n = 24) groups, receiving gavage with 0.2 mL normal saline and 400 mg/mL ceftriaxone sodium solution for 7 d (twice a day and the intermediate interval was 6 h), respectively. Then, mice in the ABx group were randomly split into three groups: model (M, 0.2 mL normal saline), low TB group (TL, 0.3 g/kg BW), and high TB group (TH, 3 g/kg BW) for 11 d. We found that TB supplementation alleviated antibiotics-induced weight loss, diarrhea, and intestinal tissue damage. The 16S rRNA sequence analysis showed that TB intervention increased the α diversity of intestinal flora, increased potential short-chain fatty acids (SCFAs)-producing bacteria (such as Muribaculaceae and Bifidobacterium), and inhibited the relative abundance of potentially pathogenic bacteria (such as Bacteroidetes and Enterococcus) compared to the M group. TB supplementation reversed the reduction in SCFAs production in antibiotic-treated mice. Additionally, TB downregulated the levels of serum LPS and zonulin, TNF-α, IL-6, IL-1β and NLRP3 inflammasome-related factors in intestinal tissue and upregulated tight junction proteins (such as ZO-1 and Occludin) and MUC2. Overall, the adjustment ability of low-dose TB to the above indexes was stronger than high-dose TB. In conclusion, TB can restore the dysbiosis of gut microbiota, increase SCFAs, suppress inflammation, and ameliorate antibiotic-induced intestinal damage, indicating that TB might be a potential gut microbiota modulator.

Dataset Information

Long-term dysbiosis and fluctuations of gut microbiome in antibiotic treated preterm infants.

Publications

Long-term dysbiosis and fluctuations of gut microbiome in antibiotic treated preterm infants.

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