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Background <p>Emerging evidence suggests that the gut microbiome plays a key role in metabolic diseases such as non-alcoholic fatty liver disease, yet the contribution of the gut mycobiome remains largely overlooked.</p> Methods <p>We performed a comprehensive analysis of publicly available fecal metagenomic sequencing data and matched serum metabolomic profiles from 90 non-alcoholic fatty liver disease patients and 90 healthy controls. A curated fungal genome database was constructed for taxonomic profiling. We integrated fungal, bacterial, and metabolomic data to assess taxon-specific associations, cross-kingdom interactions, and predictive potential.</p> Results <p>Although overall fungal diversity showed no significant differences between groups, four fungal species—<i>Pseudopithomyces</i> sp. c174, <i>Mucor</i> sp. c176, <i>Aspergillus</i> sp. c25, and <i>Ascochyta</i> c213—were significantly enriched in non-alcoholic fatty liver disease patients. The gut mycobiome explained 38.2% of the variance in serum metabolomic profiles, with several species displaying strong correlations with non-alcoholic fatty liver disease relevant metabolites. For instance, <i>Pseudopithomyces</i> sp. c174 was positively associated with protective metabolites such as glycoursodeoxycholic acid and alpha-linolenic acid, while <i>Aureobasidium</i> c170 and <i>Basipetospora</i> c193 were linked to phenylacetic acid, a metabolite implicated in hepatic lipid accumulation. Network analysis revealed altered fungal–bacterial co-abundance patterns in non-alcoholic fatty liver disease, with fungal taxa such as <i>Alternaria alternata</i> c42 and <i>Malassezia</i> c303 emerging as key hubs. A random forest classifier integrating 42 bacterial and fungal features achieved an AUC of 0.772 for distinguishing non-alcoholic fatty liver disease from controls, highlighting the predictive value of the mycobiome.</p> Conclusions <p>Our findings reveal that gut fungal communities are functionally and ecologically altered in non-alcoholic fatty liver disease and contribute to shaping the host metabolic environment. These results underscore the need to incorporate the gut mycobiome into future microbiome-based strategies for non-alcoholic fatty liver disease diagnosis and treatment.</p>

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Characterization of the gut mycobiome in patients with non-alcoholic fatty liver disease and correlations with serum metabolome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Ning Zheng,
  • Dangrang Wang,
  • Guorui Xing,
  • Yidan Gao,
  • Shenghui Li,
  • Jin Liu,
  • Jian Kang,
  • Shanshan Sha,
  • Lin Cheng,
  • Shao Fan,
  • Jian Yu,
  • Qiulong Yan,
  • Chunmeng Jiang

摘要

Background

Emerging evidence suggests that the gut microbiome plays a key role in metabolic diseases such as non-alcoholic fatty liver disease, yet the contribution of the gut mycobiome remains largely overlooked.

Methods

We performed a comprehensive analysis of publicly available fecal metagenomic sequencing data and matched serum metabolomic profiles from 90 non-alcoholic fatty liver disease patients and 90 healthy controls. A curated fungal genome database was constructed for taxonomic profiling. We integrated fungal, bacterial, and metabolomic data to assess taxon-specific associations, cross-kingdom interactions, and predictive potential.

Results

Although overall fungal diversity showed no significant differences between groups, four fungal species—Pseudopithomyces sp. c174, Mucor sp. c176, Aspergillus sp. c25, and Ascochyta c213—were significantly enriched in non-alcoholic fatty liver disease patients. The gut mycobiome explained 38.2% of the variance in serum metabolomic profiles, with several species displaying strong correlations with non-alcoholic fatty liver disease relevant metabolites. For instance, Pseudopithomyces sp. c174 was positively associated with protective metabolites such as glycoursodeoxycholic acid and alpha-linolenic acid, while Aureobasidium c170 and Basipetospora c193 were linked to phenylacetic acid, a metabolite implicated in hepatic lipid accumulation. Network analysis revealed altered fungal–bacterial co-abundance patterns in non-alcoholic fatty liver disease, with fungal taxa such as Alternaria alternata c42 and Malassezia c303 emerging as key hubs. A random forest classifier integrating 42 bacterial and fungal features achieved an AUC of 0.772 for distinguishing non-alcoholic fatty liver disease from controls, highlighting the predictive value of the mycobiome.

Conclusions

Our findings reveal that gut fungal communities are functionally and ecologically altered in non-alcoholic fatty liver disease and contribute to shaping the host metabolic environment. These results underscore the need to incorporate the gut mycobiome into future microbiome-based strategies for non-alcoholic fatty liver disease diagnosis and treatment.