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Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study

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Abstract

Background

Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy.

Methods

Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin–tazobactam) for 1 week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1 week. The PAA group received antibiotic treatment for 1 week followed by probiotics for 1 week. Fecal samples were collected at four time nodes: newborn, 1 week, 2 weeks, and 42 days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons.

Results

Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium.

Conclusions

These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits.

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Acknowledgements

We thank Majorbio Biological Technology Co., Ltd. for providing technical assistance in this study. We also thank all the parents of the neonates participated in this study.

Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81230057, 81200264, 81372615, and 81472262), the Emerging Cutting-Edge Technology Joint Research Projects of Shanghai (No. SHDC12012106), and the Tongji University Subject Pilot Program (No. 162385).

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Authors and Affiliations

  1. Department of Pediatrics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai, China

    Hui Zhong, Xiang-Geng Wang, Jing Wang, Yan-Jie Chen & Rong Yang

  2. Institute for Intestinal Diseases, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai, China

    Huan-Long Qin

Authors
  1. Hui Zhong
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  2. Xiang-Geng Wang
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Contributions

ZH performed the collection, analysis, interpretation of data and wrote the first version of manuscript. WXG, WJ and CYJ helped collect the subjects’ information and samples. YR and QHL took responsibility for the integrity of the work as a whole from study inception to the published article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rong Yang.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of Shanghai Tenth People’s Hospital (approval no. SHSY-IEC-4.0/17-42/01). Informed consent to participate in the study have been obtained from their legal guardian.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare.

Data availability

The 16S sequence information in this study has been submitted to the NCBI Sequence Read Archive (SRA), with accession number SRP115062.

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Supplementary Information

Below is the link to the electronic supplementary material.

12519_2021_443_MOESM1_ESM.tif

Supplementary file1 Supplementary Fig. 1 Dominant phyla in the NI group. NI no intervention, T0 newborn, T1 1 week, T2 2 weeks, T3 42 days after birth (TIF 999 KB)

12519_2021_443_MOESM2_ESM.tif

Supplementary file2 Supplementary Fig. 2 a Number of OTUs and the Shannon and Ace indices at T0 in the three groups; b number of OTUs and the Shannon and Ace indices at T1 and T3 in the NI and PCA groups; c dominant phyla at T1 and T3 in the NI and PCA groups (TIF 4118 KB)

12519_2021_443_MOESM3_ESM.tif

Supplementary file3 Supplementary Fig. 2 d Number of OTUs and the Shannon and Ace indices at T2 and T3 in the NI and PAA groups; e dominant phyla at T2 and T3 in the NI and PAA groups. OTU operational taxonomic units, NI no intervention, PCA probiotics used concurrently with antibiotics, PAA probiotics used after antibiotics, T0 newborn, T1 1 week, T2 2 weeks, T3 42 days after birth (TIF 3175 KB)

12519_2021_443_MOESM4_ESM.tif

Supplementary file4 Supplementary Fig. 3 a Number of OTUs and the Shannon and Ace indices at T3 in the PCA and PAA groups; b dominant phyla at T3 in the PCA and PAA groups; c key type of bacteria in the PCA group; d PCoA scores based on the relative abundance of OTUs (97% similarity level). OTU operational taxonomic units, PCA probiotics used concurrently with antibiotics, PAA probiotics used after antibiotics, LDA linear discriminant analysis, PC principal component score, PCoA principal coordinates analysis, T3 42 days after birth (TIF 2624 KB)

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Zhong, H., Wang, XG., Wang, J. et al. Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study. World J Pediatr 17, 385–393 (2021). https://doi.org/10.1007/s12519-021-00443-y

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  • DOI: https://doi.org/10.1007/s12519-021-00443-y

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