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Smoking-related Lactobacillus and immune cell infiltration in colorectal cancer: evidence from a population-based study
  1. Silu Chen1,2,3,
  2. Junyi Xin4,
  3. Dongying Gu5,
  4. Huiqin Li2,3,
  5. Rui Zheng2,3,
  6. Shuwei Li2,3,
  7. Zhengdong Zhang2,3,
  8. Mulong Du6,
  9. Meilin Wang1,2,3
  1. 1Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
  2. 2Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
  3. 3Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
  4. 4Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
  5. 5Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
  6. 6Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
  1. Correspondence to Dr Meilin Wang, Nanjing Medical University, Nanjing, Jiangsu, China; mwang{at}njmu.edu.cn

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Recently, we were intrigued by a recent study by Fong and colleagues,1 in which they found that Lactobacillus gallinarum could reduce regulatory T-cell (Treg) infiltration and enhance CD8+ T-cell effector function, thus improving anti-PD1 efficacy in patients with colorectal cancer, which was confirmed in mouse models. Interestingly, Lactobacillus was observed to be related to smoke exposure, with decreased Lactobacillus in smoke-exposed mice.2 However, the relationships between cigarette smoking, human gut microbiota and infiltration of colorectal cancer immune cells have not been determined in humans. Therefore, by leveraging large population studies, we sought to evaluate the relationship between smoking, Lactobacillus and colorectal cancer immune cell infiltration using Mendelian randomisation methods (online supplemental materials).

Supplemental material

[gutjnl-2023-331865supp001.pdf]

In this study, we first evaluated the association between smoking and Lactobacillus abundance. Although we did not observe a significant association between some smoking phenotypes (eg, Agesmk, CigDay, SmkInit and SmkIndex) and Lactobacillus, compared with former smoking, genetically predicted current smoking was borderline significantly associated with a depleted Lactobacillus (β(inverse-variance weighted (IVW))=−0.485, P=3.2×10−2; table 1), consistent with previous findings.2 Furthermore, as …

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Footnotes

  • MD and MW are joint senior authors.

  • SC, JX and DG contributed equally.

  • Contributors MW conceived, designed and revised the project. SC, JX and DG analysed the data and drafted the manuscript. HL assisted with the collection and visualisation of the data. RZ, SL and ZZ contributed to the design of methodology; MD revised and polished the manuscript. All authors contributed to the writing and review of the manuscript and approved the final manuscript for submission.

  • Funding This study was funded by National Natural Science Foundation of China (82073631, 82173601).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.