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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.

PURPOSE: To describe an alternate surgical technique for fluocinolone acetonide (Retisert) implantation in patients with extensive pars plana and pars plicata fibrosis secondary to chronic non-infectious uveitis. METHODS: This retrospective, interventional case series included five eyes of four patients who had poorly controlled chronic non-infectious uveitis. Retisert was implanted successfully using a novel approach. The device was introduced into the posterior segment through the anterior chamber and posterior capsulotomy, forgoing the need for full-thickness scleral incision and minimizing the risk of retinal detachment and associated complications. RESULTS: Five eyes underwent passage of Retisert implant through the anterior segment via a limbal incision and a posterior capsulotomy. Retisert was successfully implanted in all patients in the posterior chamber. No intraoperative or postoperative complications were encountered. Up until the last follow-up, all eyes demonstrated the stability of the implant. Visual acuity improved in four out of five eyes. CONCLUSIONS: Retisert can be implanted via the anterior chamber in patients with extensive fibrosis in the pars plana and pars plicata regions. This approach may minimize the risk of retinal traction and damage to the implant when compared to the traditional full-thickness sclerotomy method in these high-risk cases.