Integrated microbial and transcriptomic profiling reveals distinct correlations in atrophic gastritis associated with liver cirrhosis.

OBJECTIVE

To explore the alterations in the microbiota and transcriptome of patients with chronic atrophic gastritis (CAG) and liver cirrhosis (LC) and to develop robust diagnostic models.

METHODS

16S ribosomal RNA (rRNA) amplicon sequencing was performed on saliva and gastric mucosal samples, and transcriptome sequencing was performed on gastric mucosal samples from the study participants.

RESULTS

Veillonella, Ruminococcus_gnavus_group, Olsenella, and other genera were enriched in the saliva of LC patients with CAG (Cirrhosis A) compared with both LC patients without CAG (Cirrhosis N) and controls without LC (Control), while Lautropia was reduced (LDA > 2.0, adjusted P-value < 0.05). Moreover, in the independent test set, the combination of Cardiobacterium and Olsenella classified Cirrhosis A subjects from Cirrhosis N subjects with an area under the curve (AUC) of 0.89, and classified Cirrhosis A subjects from Control subjects with an AUC of 0.84. An eight-genera panel achieved an AUC of 0.92 for classifying Cirrhosis A from Control. In the gastric mucosa, ABCG5, ITGA2, MYB, and other genes were upregulated, whereas EPOR, CHAD, IGFALS, and other genes were downregulated in Cirrhosis A compared with both Cirrhosis N and CAG patients without LC (Control A) (adjusted P-value < 0.05). The overlapping differentially expressed genes were enriched, including in the PI3K-Akt signaling pathway, bile secretion, cholesterol metabolism, PPAR signaling, and steroid biosynthesis pathways. In Cirrhosis A, correlation analysis revealed that increased Aggregatibacter was positively correlated with TTC22 and PRSS3, whereas increased Allobaculum was positively correlated with TFAP2B.

CONCLUSION

LC is associated with distinct microbial and transcriptomic reprogramming in CAG, with enrichment of the PI3K-Akt signaling and bile secretion pathways, suggesting their possible involvement in cirrhosis-associated gastric mucosal changes and warranting further investigation.