Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.

The Ocular Microbiome Is Altered by Sampling Modality and Age.

Background: Studies of the ocular microbiome have used a variety of sampling techniques, but no study has directly compared different sampling methods applied to the same eyes to one another or to a reference standard of corneal epithelial biopsy. We addressed this lack by comparing the microbiome from three conjunctival swabs with those of corneal epithelial biopsy. Methods: Twelve eyes (11 patients) were swabbed by calcium alginate swab, cotton-tipped applicator, and Weck-Cel cellulose sponge before a corneal epithelial biopsy (48 samples). We then performed 16S rRNA gene sequencing and universal 16S rRNA gene real-time polymerase chain reaction. Negative/blank controls were used to eliminate contaminants. An analysis was performed to examine the concordance of the three swab types to corneal epithelial biopsy. The effect of patient age on the ocular microbiome as determined by epithelial biopsy was also examined. Results: The ocular microbiome from corneal epithelial biopsies consisted of 31 genera with a relative abundance of 1% or more, including Weisella, Corynebacterium, and Pseudomonas. Of the three swab types, Weck-Cel differed the most from corneal biopsies based on beta-diversity analysis. Cotton swabs were unable to capture the Bacteroides population seen on epithelial biopsy. Therefore, calcium alginate swabs seemed to be the closest to epithelial biopsies. Older patients (≥65 years old) had higher alpha diversity (P < 0.05) than younger patients. Differential abundance testing showed that there were 18 genera that were differentially abundant between the two age groups, including Streptococcus and eight members of the Proteobacteria phylum. Conclusions: We demonstrate that ocular sampling method and patient age can greatly affect the outcome of sequencing-based analysis of the ocular microbiome. Translational Relevance: By understanding the impact of different sampling methods on the results obtained from the ocular surface microbiome, future research on the topic will be more reproducible, leading to a better understanding of ocular surface microbiome in health and disease.

Gut microbiome profiles associated with steatosis severity in metabolic associated fatty liver disease.

Aim: The microbiome has been shown to be pivotal in the development of metabolic associated fatty liver disease (MAFLD). Few have examined the relationship of the microbiome specifically with steatosis grade. Therefore, our aim was to characterize the association of the microbiome with MAFLD steatosis severity while adjusting for metabolic comorbidities including diabetes. Methods: We enrolled patients with MAFLD at the West Los Angeles Veterans Affair Hospital. All patients underwent ultrasound elastography, fasting serum collection, and fecal sampling for 16S sequencing. We examined the associations of microbial diversity and composition with advanced steatosis, defined as a CAP score of ≥ 300 dB/m, with or without the presence of metabolic comorbidities. Results: Seventy-five patients were enrolled. African American were less likely to have advanced steatosis than either Hispanics or Whites (P = 0.001). Patients with more advanced steatosis had higher fasting serum triglyceride (192.6 ± 157.1 mg/dL vs. 122.5 ± 57.4 mg/dL), HbA1c (6.7% ± 1.4% vs. 6.1% ± 0.8%), transaminases, and were more likely to have metabolic syndrome (52.4% vs. 24.2%, P = 0.02). Advanced steatosis and diabetes were associated with altered microbial composition. Bacteroides was negatively associated with advanced steatosis while Megasphaera was positively associated with steatosis. Akkermansia was negatively associated with diabetes, while Anaerostipes and Parabacteroides were positively associated with diabetes. Conclusion: Diabetes and metabolic syndrome are associated with hepatic steatosis severity in MAFLD patients and both advanced steatosis and comorbid diabetes are independently associated with microbiome changes. These results provide insight into the role of the gut microbiome in MAFLD associated with metabolic syndrome.