Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology

Yasmina Tashkent; Jocelyn M Choo; Alyson Richard; Zhengyi Wang; Luis Calzadilla-Bertot; Egi Vasil; Sophie Miller; Steven L Taylor; Kerry L Ivey; Richard Woodman; Brendan Adler; Oyekoya T Ayonrinde; John K Olynyk; Lawrence J Beilin; Trevor A Mori; Alan J Wigg; Kate R Muller; Leon A Adams; Geraint B Rogers

doi:10.1111/liv.70032

Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology

Yasmina Tashkent, Jocelyn M Choo, Alyson Richard, Zhengyi Wang, Luis Calzadilla-Bertot, Egi Vasil, Sophie Miller, Steven L Taylor, Kerry L Ivey, Richard Woodman, Brendan Adler, Oyekoya T Ayonrinde, John K Olynyk, Lawrence J Beilin, Trevor A Mori, Alan J Wigg, Kate R Muller, Leon A Adams, Geraint B Rogers

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.

METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).

CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.

TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).

Original language	English
Article number	e70032
Number of pages	13
Journal	Liver International
Volume	45
Issue number	3
DOIs	https://doi.org/10.1111/liv.70032
Publication status	Published - Mar 2025

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10.1111/liv.70032Licence: CC BY-NC-ND

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Tashkent, Y., Choo, J. M., Richard, A., Wang, Z., Calzadilla-Bertot, L., Vasil, E., Miller, S., Taylor, S. L., Ivey, K. L., Woodman, R., Adler, B., Ayonrinde, O. T., Olynyk, J. K., Beilin, L. J., Mori, T. A., Wigg, A. J., Muller, K. R., Adams, L. A., & Rogers, G. B. (2025). Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology. Liver International, 45(3), Article e70032. https://doi.org/10.1111/liv.70032

@article{f2c930faf68343438f595869bd31b23e,

title = "Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology",

abstract = "BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).",

keywords = "Humans, Gastrointestinal Microbiome, Male, Adult, Female, Cross-Sectional Studies, Feces/microbiology, Magnetic Resonance Imaging, Fatty Liver/microbiology",

author = "Yasmina Tashkent and Choo, {Jocelyn M} and Alyson Richard and Zhengyi Wang and Luis Calzadilla-Bertot and Egi Vasil and Sophie Miller and Taylor, {Steven L} and Ivey, {Kerry L} and Richard Woodman and Brendan Adler and Ayonrinde, {Oyekoya T} and Olynyk, {John K} and Beilin, {Lawrence J} and Mori, {Trevor A} and Wigg, {Alan J} and Muller, {Kate R} and Adams, {Leon A} and Rogers, {Geraint B}",

note = "{\textcopyright} 2025 The Author(s). Liver International published by John Wiley & Sons Ltd.",

year = "2025",

month = mar,

doi = "10.1111/liv.70032",

language = "English",

volume = "45",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "3",

}

Tashkent, Y, Choo, JM, Richard, A, Wang, Z, Calzadilla-Bertot, L, Vasil, E, Miller, S, Taylor, SL, Ivey, KL, Woodman, R, Adler, B, Ayonrinde, OT, Olynyk, JK, Beilin, LJ , Mori, TA, Wigg, AJ, Muller, KR, Adams, LA & Rogers, GB 2025, 'Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology', Liver International, vol. 45, no. 3, e70032. https://doi.org/10.1111/liv.70032

TY - JOUR

T1 - Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology

AU - Tashkent, Yasmina

AU - Choo, Jocelyn M

AU - Richard, Alyson

AU - Wang, Zhengyi

AU - Calzadilla-Bertot, Luis

AU - Vasil, Egi

AU - Miller, Sophie

AU - Taylor, Steven L

AU - Ivey, Kerry L

AU - Woodman, Richard

AU - Adler, Brendan

AU - Ayonrinde, Oyekoya T

AU - Olynyk, John K

AU - Beilin, Lawrence J

AU - Mori, Trevor A

AU - Wigg, Alan J

AU - Muller, Kate R

AU - Adams, Leon A

AU - Rogers, Geraint B

PY - 2025/3

Y1 - 2025/3

N2 - BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).

AB - BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).

KW - Humans

KW - Gastrointestinal Microbiome

KW - Male

KW - Adult

KW - Female

KW - Cross-Sectional Studies

KW - Feces/microbiology

KW - Magnetic Resonance Imaging

KW - Fatty Liver/microbiology

U2 - 10.1111/liv.70032

DO - 10.1111/liv.70032

M3 - Article

C2 - 39999013

SN - 1478-3223

VL - 45

JO - Liver International

JF - Liver International

IS - 3

M1 - e70032

ER -

Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology

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Measuring breast density in younger women to inform primary prevention and early detection of breast cancer

Predicting Obstructive Sleep Apnoea using 3D Craniofacial Photography

Genetic And Early Life Predictors Of Ectopic Fat And Their Association With Cardiometabolic Health And Disease

Cite this