RESUMEN
Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs and increased complications of many diseases including SARS-CoV-2 infection. The Western Diet (WD) specifically is believed to be a major contributor to the global metabolic disease epidemic. In contrast, the Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) are often considered beneficial for metabolic health. Yet, there is a growing appreciation that the effect of diet on metabolic health varies depending on several factors including host genetics. Additionally, poor metabolic health has also been attributed to altered gut microbial composition and/or function. To understand the complex relationship between host genetics, gut microbiota, and dietary patterns, we treated four widely used metabolically diverse inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) with four human-relevant diets (MeD, JD, KD, WD), and a control mouse chow from 6 weeks to 30 weeks of age. We found that diet-induced alteration of gut microbiota (α-diversity, ß-diversity, and abundance of several bacteria including Bifidobacterium, Ruminococcus, Turicibacter, Faecalibaculum, and Akkermansia) is significantly modified by host genetics. In addition, depending on the gut microbiota, the same diet could have different metabolic health effects. Our study also revealed that C57BL/6J mice are more susceptible to altered gut microbiota compared to other strains in this study indicating that host genetics is an important modulator of the diet-microbiota-metabolic health axis. Overall, our study demonstrated complex interactions between host genetics, gut microbiota, and diet on metabolic health; indicating the need to consider both host genetics and the gut microbiota in the development of new and more effective precision nutrition strategies to improve metabolic health.
RESUMEN
BACKGROUND: Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals. AIMS: To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed. METHODS: Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone. Cessation of rectal bleeding (RB) was defined as absence of bleeding on four consecutive days. Endoscopic remission was defined as DAI mucosal healing (MH) subscore=0 and clinical remission as MH subscore =0-1 and ≥ 1-point improvement, plus RB subscore = 0. RESULTS: Study I: By Day 2, 31.4% of subjects using topical monotherapy reported no RB vs. 5.5% in the placebo arm (P<0.0006); median time to RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs. 7.8%, P<0.005) and clinical remission (48.6% vs. 9.6%, P<0.0001) were observed at Week 3. Study II: A significantly higher proportion of subjects achieved RB cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week 3, a significantly higher proportion of subjects using combination therapy achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%, P<0.05). CONCLUSIONS: Topical mesalazine suspension, either alone or in combination with oral mesalazine, led to earlier rectal bleeding cessation and mucosal healing. These data support use of topical therapy for more rapid treatment benefit in active distal ulcerative colitis.
