Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective:To investigate the measurements of the ciliary body in patients with acute primary angle-closure (APAC).Methods:This was a case-control study.Subjects were admitted to Ningxia Eye Hospital from January to October 2016.Fifty-five consecutive patients diagnosed with APAC in one eye were presented as case groups, and their fellow eyes were presented as fellow groups.Fifty-five eyes from 55 age-matched normal controls were also recruited as control groups.A-scan ultrasonography and ultrasound biomicroscopy (UBM) were conducted to determine biometric measurements and ciliary body parameters.Biometric measurements included axial length (AL), lens thickness (LT), anterior chamber depth (ACD), pupil diameter (PD), anterior chamber width (ACW) and lens vault (LV). Ciliary body parameters included maximum ciliary body thickness (CBTmax), ciliary body thickness at the point of the scleral spur (CBT 0) and 1 000 μm from the scleral spur (CBT 1000), anterior placement of the ciliary body (APCB), and trabecular-ciliary process angle (TCA), respectively.Pearson correlation analysis was used to examine the correlation between the biometric measurements and the ciliary body parameters.Written informed consent was obtained from each subject before any medical examination.The study protocol was approved by the Ethics Committee of People's Hospital of Ningxia Hui Autonomous Region. Results:The ACD was smaller, while the PD and lens thickness were larger in eyes with APAC compared with their fellow eyes.The differences were statistically significant ( t=-6.805, 3.490, 2.624; all at P<0.05). Smaller AL and ACD measurements were found in the fellow eyes of APAC patients compared with normal eyes, and these differences were statistically significant ( t=-4.828, -6.947; both at P<0.001). For eyes with APAC, their fellow eyes and normal eyes, the average CBT max were (0.907±0.106), (0.960±0.098) and (1.020±0.108)mm; average TCA were (48.99±11.48)°, (51.32±10.87)° and (81.94±12.45)°, respectively.CBT max, CBT 0, CBT 1000, and TCA measukements were smaller, and APCB were larger in eyes with APAC compared with their fellow eyes, and these differences were statistically significant ( t=-5.354, -3.517, -3.407, -0.753; all at P<0.05). In addition, CBT max, CBT 0, CBT 1000, and TCA measurements were smaller, and APCB were larger in the fellow eyes compared with the normal eyes, these differences were also statistically significant ( t=-6.040, -3.132, -6.005, -13.509, 16.795; all at P<0.05). Positive correlations were found between AL and CBT 1000, and between AL and TCA ( r=0.335, P=0.012; r=0.380, P=0.004), while a negative correlation was found between intraocular pressure and CBTmax ( r=-0.289, P=0.032). Conclusions:In eyes with APAC, as well as their fellow eyes, ciliary bodies are thinner and anteriorly rotated, and this anatomical change is associated with shorter AL and high intraocular pressure.