Ciprofloxacin utilization and reversible nanoscale morphological transition in Klebsiella sp. SG01

Ganguli, Sriradha

doi:10.1016/j.procbio.2026.03.009

Generative AI-augmented transcriptomic and microbiome analysis across inflammatory and fibrotic disease states in Crohn’s disease

2026-08-05

0

OA

AI

D

DP Daryll Philip †

D

DS Daniela Santos †

S

SM Sudip Mondal †

H

HA Haneen Alomar

G

Georgios V. Gkoutos

A

AA Animesh Acharjee *

DOI：10.3389/frai.2026.1881820

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IntroductionIntestinal fibrosis is a major complication of Crohn’s disease (CD); a subtype of inflammatory bowel disease (IBD) driven by chronic inflammation and resulting in irreversible structural damage requiring surgery. However; the molecular differences between inflammatory and fibrotic CD remain poorly defined.MethodsHere; we developed an integrated multi-omics framework combining transcriptomics; microbiome analysis; and generative AI to characterise transcriptomic differences across non-IBD (n = 176); baseline CD (n = 187); and fibrosis CD (n = 85) tissues. Bulk and single-cell RNA-seq and 16S rRNA datasets were integrated; and machine learning identified disease-stage associated features.ResultsA shared set of 43 genes between baseline and fibrotic CD was organised into three modules: Module 1 (S100A8; TREM1; CXCL1) linked to innate immune activation which was upregulated in fibrosis CD; Module 2 (FABP6; MGAM; ALDOB) reflecting epithelial metabolic dysfunction which was upregulated in baseline CD; and Module 3 (CHI3L1; SAA2-SAA4; IL1RN) associated with epithelial stress and loss of barrier integrity. GSVA highlighted LCN2 and MMP3 across disease states. Microbiome analysis showed depletion of SCFA-producing genera (Faecalibacterium; Anaerostipes; Coprococcus; Ruminococcus) and enrichment of Bilophila and Bacteroides. Notably; LLM-guided augmentation improved model stability and facilitated the identification of key fibrosis-associated genes; including IL-23R; TNF-α; and TGF-β.DiscussionThese findings suggest that intestinal fibrosis in CD does not represent a separate molecular state; but a reconfigured inflammatory condition characterised by persistent immune activation; epithelial dysfunction; and altered host-microbiome interactions.

Keywords:

machine learning

microbiome

inflammatory bowel disease

transcriptomics

generative AI

Crohn’s disease

fibrosis

large language modelling

Generative AI-augmented transcriptomic and microbiome analysis across inflammatory and fibrotic disease states in Crohn’s disease

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