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Microbes & Immunity Hydrogen alleviates non-alcoholic fatty liver disease

the transcriptional basis in this regard remains unknown. Writing–original draft: Yu Wang, Youzhen Wei
Thus, characterizing the complete gene-expression Writing–review & editing: Fan Zhang, Jianjun Zhou
profile in hepatocytes and stromal cells in the liver with
and without H treatment will be critical to a better Ethics approval and consent to participate
2
understanding of the exact mechanisms. Furthermore, All animal studies were approved by the Institutional
although A. muciniphila seems to be the critical middle Animal Care and Use Committee of the Tongji University
factor in mediating H -induced NAFLD reversal in terms Affiliated East Hospital (T3LAC-015-038).
2
of symptoms and biochemistry, other bacteria may also
play a role. Further work will be needed to determine to Consent for publication
what extent A. muciniphila, on its own, could influence Data are available from the corresponding author upon
the NAFLD pathogenic process. Finally, the animal reasonable request.
experiments substantiated the beneficial effects of H
2
treatment on FBR and A. muciniphila abundance, but Availability of data
the exact mechanism regarding how H affects the gut
2
microbiota remains to be unveiled. Not applicable.
5. Conclusion References

In summary, these results provide a better understanding 1. Isaacs S. Nonalcoholic fatty liver disease. Endocrinol Metab
of the effects and possible mechanisms of H treatment Clin North Am. 2023;52(1):149-164.
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in mice with NAFLD. In fact, H is naturally present in doi: 10.1016/j.ecl.2022.06.007
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the colon due to anaerobic bacterial fermentation, and 2. Byrne CD, Targher G. NAFLD: A multisystem disease.
its abundance is important for maintaining a healthy J Hepatol. 2015;62:S47-S64.
anaerobic ecosystem. H delivery by direct inhalation doi: 10.1016/j.jhep.2014.12.012
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or the transplantation of engineered H -producing
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A. muciniphila is two attractive approaches to pursue 3. Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver
in translational medicine. We demonstrated that the disease: A multisystem disease requiring a multidisciplinary
gut microbiota can be safely and positively altered by and holistic approach. Lancet Gastroenterol Hepatol.
H administration. Thus, H has promising therapeutic 2021;6(7):578-588.
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potential for NAFLD by increasing the abundance of A. doi: 10.1016/S2468-1253(21)00020-0
muciniphila, although H therapy is fraught with several 4. Mundi MS, Velapati S, Patel J, Kellogg TA, Abu Dayyeh BK,
2
clinical limitations, including the involvement of adequate Hurt RT. Evolution of NAFLD and its management. Nutr
and expensive medical facilities. Clin Pract. 2020;35(1):72-84.
Acknowledgments doi: 10.1002/ncp.10449
5. Paredes-Turrubiarte G, González-Chávez A,
We thank Dr. Wenjie Tang for her critical scientific support.
Pérez-Tamayo R, et al. Severity of non-alcoholic fatty liver
Funding disease is associated with high systemic levels of tumor
necrosis factor alpha and low serum interleukin 10 in
This study was supported by the Small and Micro Science morbidly obese patients. Clin Exp Med. 2016;16(2):193-202.
and Technology Project grant (No. 20004) of the National doi: 10.1007/s10238-015-0347-4
Health Commission, and the Shanxi Provincial Natural
Fund Project (202203021211239). 6. Chelakkot C, Choi Y, Kim DK, et al. Akkermansia
muciniphila-derived extracellular vesicles influence gut
Conflict of interest permeability through the regulation of tight junctions. Exp
Mol Med. 2018;50:e450.
The authors declare they have no competing interests.
doi: 10.1038/emm.2017.282
Author contributions 7. Everard A, Belzer C, Geurts L, et al. Cross-talk between
Akkermansia muciniphila and intestinal epithelium
Conceptualization: Yu Wang, Youzhen Wei controls diet-induced obesity. Proc Natl Acad Sci U S A.
Formal analysis: Jianjun Zhou, Yunxi Chen 2013;110(22):9066-9071.
Investigation: Yu Wang, Fan Zhang, Yan Tian, Jianjun Zhou
Methodology: Yu Wang, Fan Zhang, Yan Tian, Yunxi Chen, doi: 10.1073/pnas.1219451110
Youzhen Wei 8. Ondee T, Pongpirul K, Visitchanakun P, et al. Lactobacillus

Volume 1 Issue 2 (2024) 78 doi: 10.36922/mi.3896