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Translational Therapeutics

Early life Lactobacillus rhamnosus GG colonisation inhibits intestinal tumour formation

British Journal of Cancer volume 126, pages 1421–1431 (2022)Cite this article

Subjects

Abstract

Background

Gut microbiota dysbiosis is closely related to the progression of colorectal cancer. Our previous study revealed that early life colonisation with Lactobacillus rhamnosus GG (LGG) had long-term positive effects on health. We sought to investigate whether early life LGG colonisation could inhibit intestinal tumour formation in offspring.

Methods

Adult C57BL/6 female mice were mated with Apcmin/+ male mice. Pregnant mice with the same conception date received 108 cfu live or fixed LGG from day 18 of pregnancy until natural delivery. After genotyping, offspring mice received 107 cfu of live or fixed LGG for 0–5 days after birth.

Results

Early life LGG colonisation significantly promoted intestinal development, inhibited low-grade intestinal inflammation and altered the gut microbiota composition of offspring in the weaning period (3 week old). Notably, early life LGG colonisation reduced the multiplicity of intestinal tumours in adulthood (12 week old), possibly due to inhibition of Wnt signalling and promotion of tumour cell apoptosis. Importantly, at the genus level, Bifidobacterium and Anaeroplasma with potential anti-tumour effects were increased in adulthood, while Peptostreptococcus, which potentially contributes to tumour formation, was decreased.

Conclusions

Early life LGG colonisation inhibited the intestinal tumour formation of offspring in adulthood.

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Fig. 1: Experiment process and LGG colonisation detection.
Fig. 2: Early life LGG colonisation promoted intestinal development of 3-week-old offspring.
Fig. 3: Early life LGG colonisation promoted intestinal barrier of 3-week-old mice.
Fig. 4: Early life LGG colonisation inhibited intestinal tumour formation and promote tumour cell apoptosis of Apcmin/+FCCC offspring in adulthood.
Fig. 5: Early life LGG colonisation inhibited Wnt signaling pathway of Apcmin/+FCCC offspring in adulthood.
Fig. 6: Early life LGG colonisation altered the composition and diversity of gut microbiota in 12-week-old offspring mice.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to the reviewers for their constructive suggestions to improve the earlier version of this manuscript.

Funding

This research was supported by grants (82070545, 82000511 and 81970477) from the National Natural Science Foundation of China, the Key Project of Science and Technology Pillar Program of Tianjin (20YFZCSY00020) and the Zhao Yicheng Medical Science Foundation Youth Incubation Project of Tianjin (ZYYFY2019018).

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  1. These authors contributed equally: Xiang Liu, Ge Jin.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China

    Xiang Liu, Ge Jin, Qiang Tang, Shumin Huang, Yue Sun, Tianyu Liu, Zixuan Guo, Bangmao Wang, Kui Jiang, Weilong Zhong & Hailong Cao

  2. Department of Pathology, General Hospital, Tianjin Medical University, Tianjin, China

    Yujie Zhang

  3. Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China

    Cheng Yang & Hailong Cao

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Contributions

XL, GJ, CY, BMW, WLZ, KJ and HLC were involved in the study design, XL, GJ, QT, SMH, YS, TYL and ZXG performed the experiments. XL, GJ, YJZ, QT, KJ and HLC analysed the data. XL, GJ and HLC wrote the manuscript. KJ, WLZ and HLC made the critical revisions. XL, GJ and HLC were aware of the group allocation in the experiment. All authors contributed to the design and writing of the paper and agreed with the final version of the content of the manuscript.

Corresponding authors

Correspondence to Kui Jiang, Weilong Zhong or Hailong Cao.

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The authors declare no competing interests.

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All experimental procedures were performed according to the International Association of Veterinary Editors guidelines for the Care and Use of Laboratory Animal protocols and approved by the Institutional Animal Care and Use Committee at Tianjin Medical University, Tianjin, P. R. China.

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Liu, X., Jin, G., Tang, Q. et al. Early life Lactobacillus rhamnosus GG colonisation inhibits intestinal tumour formation. Br J Cancer 126, 1421–1431 (2022). https://doi.org/10.1038/s41416-021-01562-z

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