@article{Forlano:2024:10.1080/19490976.2024.2304157,
author = {Forlano, R and Martinez-Gili, L and Takis, P and Miguens-Blanco, J and Liu, T and Triantafyllou, E and Skinner, C and Loomba, R and Thursz, M and Marchesi, JR and Mullish, BH and Manousou, P},
doi = {10.1080/19490976.2024.2304157},
journal = {Gut Microbes},
title = {Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.},
url = {http://dx.doi.org/10.1080/19490976.2024.2304157},
volume = {16},
year = {2024}
}

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TY  - JOUR
AB  - Aberration of the "gut-liver axis" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.
AU  - Forlano,R
AU  - Martinez-Gili,L
AU  - Takis,P
AU  - Miguens-Blanco,J
AU  - Liu,T
AU  - Triantafyllou,E
AU  - Skinner,C
AU  - Loomba,R
AU  - Thursz,M
AU  - Marchesi,JR
AU  - Mullish,BH
AU  - Manousou,P
DO  - 10.1080/19490976.2024.2304157
PY  - 2024///
TI  - Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.
T2  - Gut Microbes
UR  - http://dx.doi.org/10.1080/19490976.2024.2304157
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38235661
UR  - http://hdl.handle.net/10044/1/109240
VL  - 16
ER  - 

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