Hum Mutat. 2026 May 21;2026:6434376. doi: 10.1155/humu/6434376. eCollection 2026.

ABSTRACT

Immune checkpoint inhibitors have become integral to the management of non-small cell lung cancer (NSCLC), yet both primary and acquired resistance remain frequent and are only partially captured by routine biomarkers such as programmed death-ligand 1 (PD-L1) immunohistochemistry and tumor mutational burden (TMB). Resistance is increasingly viewed as a multiaxis functional phenotype shaped by antigenicity and neoantigen quality, antigen processing and presentation competence, interferon signaling and adaptive resistance programs, tumor-immune spatial organization, suppressive myeloid/stromal ecosystems, and metabolic constraints that limit effector function. Multiomics profiling provides a practical route to translate genomic event anchors into reproducible, mechanistically interpretable biomarker outputs by assembling coherent evidence chains across genomics, transcriptomics, epigenomics, proteomics, and metabolomics, complemented by spatial assays, digital pathology, and imaging-derived surrogates.

PMID:42181742 | PMC:PMC13191777 | DOI:10.1155/humu/6434376

Probiotics Antimicrob Proteins. 2026 May 23. doi: 10.1007/s12602-026-11062-2. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease with a rising global incidence. The treatment of AIH remains challenging because first-line drugs show limited efficacy and systemic side effects. Gut microbiota plays a crucial role in the pathogenesis of AIH, leading to growing interest in developing probiotic-based therapies. In this study, we used multi-omics analysis to investigate the therapeutic effects of a quadruple probiotic mixture (Probiotic-quad) consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus in a well-established chronic AIH murine model. Our results showed that Probiotic-quad treatment significantly alleviated AIH progression, as evidenced by lower serum liver enzyme levels, ameliorated hepatic inflammatory infiltration and histopathological damage. Metagenomic sequencing results showed that gut dysbiosis in AIH mice was partially reversed after Probiotic-quad administration. Additionally, the integrity of the intestinal epithelial barrier was restored, accompanied by a reduction in serum lipopolysaccharide levels. Untargeted metabolomic and transcriptomic analysis revealed that Probiotic-quad treatment was linked to alterations in hepatic metabolism, including the citrate cycle and tryptophan metabolism, and was associated with reduced activation of the NF-κB and NOD-like receptor signaling pathways. These findings suggest that Probiotic-quad treatment ameliorates AIH severity and is potentially associated with changes in hepatic immune responses, metabolism, gut microbiota, and intestinal barrier function, highlighting its potential as an adjuvant therapy for AIH.

PMID:42176246 | DOI:10.1007/s12602-026-11062-2