Microbiome and gut-liver interactions: From mechanisms to therapies

Table 1 Personalized therapies targeting microbial and genetic profiles

Innovation/strategy	Description	Example	Ref.
FUT2 genotype-based interventions	Personalized treatment based on FUT2 secretor status to prevent fungal dysbiosis and strictures	Early antifungal treatment in FUT2 non-secretors with PSC	Rupp et al[7]
Bacteriophage therapy	Use of genetically modified bacteria or bacteriophages to restore healthy microbiota and reduce pathogens	Targeting Klebsiella pneumoniae and Enterococcus in PSC to reduce Th17-driven inflammation	Ichikawa et al[9]
Inflammasome inhibitors	Suppress cholangiocyte inflammasome activation and IL-1β release	OLT1177 in experimental models	Yao et al[10]
Genomic profiling and targeted therapy	Tailoring treatment based on tumor or patient genetic mutations	FGFR2-selective tyrosine kinase inhibitors for advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement, and an IDH1 inhibitor for IDH1-mutated cholangiocarcinoma	Khosla et al[109]
Bile acid receptor agonists	Modulate bile acid synthesis and secretion to reduce cholestasis and liver injury	Intercept INT-767 (dual FXR/TGR5 receptor agonist) maralixibat (selective ileal bile acid transporter inhibitor)	Baghdasaryan et al[2]; Bowlus et al[110]
Peroxisome proliferator activated receptor (PPAR) α/δ agonists	Reduce bile acid synthesis, inflammation, and fibrosis	Elafibranor (dual PPARα/δ agonist) and seladelpar (PPAR δ agonist) are FDA approved. Saroglitazar (dual PPARα/γ agonist) in clinical trials	Saeedian et al[111]
Multi-omics integration	Integration of genomics, metabolomics, and microbiomics to stratify patients and optimize therapy	Potential of multi-omics-based classification to inform prognosis and guide pre- and postoperative therapeutic decisions	Alaimo et al[112]

PPAR: Peroxisome proliferator activated receptor; FGFR2: Fibroblast growth factor receptor 2; IDH1: Isocitrate dehydrogenase 1; IL: Interleukin; PSC: Primary sclerosing cholangitis; FXR: Farnesoid X receptor; TGR5: Takeda G protein-coupled bile acid receptor 5; FDA: Food and Drug Administration.