The gut and lung microbiota in pulmonary tuberculosis: susceptibility, function, and new insights into treatment

ABSTRACTIntroduction Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a major threat to human health.Areas covered Herein, we aim to review the alteration of the microbiota in gut and respiratory during TB development, the potential function and mechanisms of microbiota in the pathogenesis of Mtb infection, and the impact of antibiotic treatment on the microbiota. In addition, we discuss the potential new paradigm for the use of microbiota-based treatments such as probiotics and prebiotics in the treatment of TB.Expert opinion Studies have shown that trillions of micro-organisms live in the human gut and respiratory tract, acting as gatekeepers in maintaining immune homeostasis and respiratory physiology, and playing a beneficial or hostile role in the development of TB. Anti-TB antibiotics may cause microecological imbalances in the gut and respiratory tract, and microbiome-based therapeutics may be a promising strategy for TB treatment. Appropriate probiotics and prebiotics supplementation, along with antimycobacterial treatment, will improve the therapeutic effect of TB treatment and protect the gut and respiratory microbiota from dysbiosis.KEYWORDS: DysbiosisgutlungmicrobiotatuberculosisDisclaimerAs a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also. Article highlightsTB or anti-TB contributed to decreased microbial diversity in the gut and lung.Microbiota affects susceptibility to TB by regulating inflammation and immunity.Gut -lung axis microbiome variability may affect individual response to vaccines.Maintenance of gut microbiota homeostasis may be beneficial for host recovery and prevention of recurrent Mtb infection.Microbiota-based interventions such as probiotics and prebiotics could serve as a potential advantageous supplementary approach to TB therapy.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Ethics statementThis study was approved by the ethics committee of the Baoan People's Hospital of Shenzhen (approval no. BYL20220611).Data availability statementThe datasets generated or analyzed during this study are available in the PubMed.AcknowledgementsWe thank the reviewers for their valuable suggestions. Figures were created with BioRender.com.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Authors' contributionsQZ: Conceptualization, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft. XZ: Supervision, Writing - original draft and Writing - review and editing. CC and KZ: Supervision and Software. YX: Conceptualization, Project administration, Resources, Supervision and Writing - review and editing.Additional informationFundingThis paper was funded by the Ministry of Science and Technology of the People's Republic of China, National Natural Science Foundation of China (82000017), Guangdong Provincial Department of Science and Technology, Natural Science Foundation of Guangdong Province (2022A1515012438), Science, Technology and Innovation Commission of Shenzhen Municipality, Natural Science Foundation of Shenzhen Municipality (JCY20220530142801003).This work was supported by the National Natural Science Foundation of China under grant number 82000017; Natural Science Foundation of Guangdong Province under grant number 2022A1515012438; and Natural Science Foundation of Shenzhen under grant number JCY20220530142801003.