Quebec Heart and Lung Institute (Iucpq), Faculty of Medicine, and Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, Canada.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gut Microbes. 2021 Jan-Dec;13(1):1988836. doi: 10.1080/19490976.2021.1988836.
Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity and insulin resistance. Host defense peptides (HDPs) are key regulators of gut homeostasis and generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function in diet-induced obesity and chemically induced colitis through daily oral administration of lysozyme, a well-characterized HDP, derived from .C57BL6/J mice were fed either low-fat reference diet or HFD ± daily gavage of lysozyme for 12 weeks, followed by metabolic assessment and evaluation of colonic microbiota encroachment. To further evaluate the efficacy of intestinal inflammation, we next supplemented chow-fed BALB/c mice with lysozyme during Dextran Sulfate Sodium (DSS)-induced colitis in either conventional or microbiota-depleted mice. We assessed longitudinal microbiome alterations by 16S amplicon sequencing in both models.Lysozyme dose-dependently alleviated intestinal inflammation in DSS-challenged mice and further protected against HFD-induced microbiota encroachment and fasting hyperinsulinemia. Observed improvements of intestinal health relied on a complex gut flora, with the observation that microbiota depletion abrogated lysozyme's capacity to mitigate DSS-induced colitis. associated with impaired gut health in both models, a trajectory that was mitigated by lysozyme administration. In agreement with this notion, PICRUSt2 analysis revealed specific pathways consistently affected by lysozyme administration, independent of vivarium, disease model and mouse strain.Taking together, lysozyme leveraged the gut microbiota to curb DSS-induced inflammation, alleviated HFD-induced gastrointestinal disturbances and lowered fasting insulin levels in obese mice. Collectively, these data present derived lysozyme as a promising candidate to enhance gut health.
结肠炎的特征是结肠炎症和肠道健康受损。这两个特征都加重了肥胖和胰岛素抵抗。宿主防御肽（HDPs）是肠道内稳态的关键调节剂，通常在上述情况下功能失调。我们旨在通过每天口服来自.C57BL6/J 小鼠的溶菌酶来改善饮食诱导的肥胖和化学诱导的结肠炎中的肠道功能。C57BL6/J 小鼠被喂食低脂参考饮食或 HFD ± 每天胃内给予溶菌酶 12 周，随后进行代谢评估和结肠微生物群侵袭评估。为了进一步评估肠道炎症的疗效，我们在下一个实验中在葡聚糖硫酸钠（DSS）诱导的结肠炎期间在常规或微生物群耗竭的 BALB/c 小鼠中补充了溶菌酶。我们通过 16S 扩增子测序在这两种模型中评估了纵向微生物组的变化。溶菌酶剂量依赖性地减轻了 DSS 挑战的小鼠的肠道炎症，并进一步防止了 HFD 诱导的微生物群侵袭和禁食高胰岛素血症。观察到的肠道健康改善依赖于复杂的肠道菌群，观察到微生物群耗竭消除了溶菌酶减轻 DSS 诱导的结肠炎的能力。与两种模型中的肠道健康受损有关，这一轨迹通过溶菌酶给药得到缓解。与这一观点一致，PICRUSt2 分析显示了特定的途径，这些途径一致受到溶菌酶给药的影响，独立于动物房、疾病模型和小鼠品系。总之，溶菌酶利用肠道微生物群来抑制 DSS 诱导的炎症，缓解 HFD 诱导的胃肠道紊乱，并降低肥胖小鼠的空腹胰岛素水平。总的来说，这些数据表明衍生的溶菌酶是增强肠道健康的有前途的候选药物。
