Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
Pancreatology. 2022 Jan;22(1):30-42. doi: 10.1016/j.pan.2021.12.003. Epub 2021 Dec 16.
Chronic pancreatitis (CP) is an inflammatory disease of the pancreas with loss of exocrine/endocrine functions as well as development of fibrosis. Dysbiosis of gut microbiome has been shown to be involved in the pathogenesis of many disease processes. Therefore, we aim to investigate the alteration in gut microbiome associated with CP in caerulein-induced mouse model.
CP was induced in C57Bl/6 by using caerulein injections (50 μg/kg/h, i.p., x7, twice weekly for 10 weeks). Stool samples were collected either one week after end of injection (10-week CP) or 6 weeks (16-week CP). DNA was extracted from stool samples and V4 region of 16S rDNA was sequenced for microbiome analysis.
CP was strongly associated with the alteration in the composition of the gut microbiome, evidenced by differences in α and β diversity. When β diversity was measured using both weighted and unweighted UniFrac distances, stool from control mice is significantly different from mice on 10-week or 16-week CP (q < 0.01). The α-diversity measured by Faith's phylogenetic diversity was lowest in stool from healthy control and highest in stool from mice with 16-week CP (p < 0.001). Bacteria taxa differentially enriched in CP samples were detected using linear discriminant analysis. Bacteria from genera Bifidobacterium, Akkermansia, and Desulfovibrio were enriched in samples from 10-week CP mice. Bacteria from genera Allobaculum, Prevotella, and Bacteroides were enriched in samples from 16-week CP mice.
Together, these analyses reveal pronounced alteration in the gut microbiome composition, diversity, and function when mice develop CP.
慢性胰腺炎（CP）是一种胰腺炎症性疾病，表现为外分泌/内分泌功能丧失和纤维化发展。肠道微生物组的失调已被证明与许多疾病的发病机制有关。因此，我们旨在研究胆胰酶诱导的小鼠模型中与 CP 相关的肠道微生物组的改变。
使用胆胰酶（50μg/kg/h，腹腔内注射，x7，每周两次，共 10 周）诱导 C57Bl/6 小鼠发生 CP。在注射结束后 1 周（10 周 CP）或 6 周（16 周 CP）采集粪便样本。从粪便样本中提取 DNA，并对 16S rDNA 的 V4 区进行测序进行微生物组分析。
CP 与肠道微生物组组成的改变密切相关，表现在 α 和 β 多样性的差异。当使用加权和非加权 UniFrac 距离测量 β 多样性时，来自对照小鼠的粪便与 10 周或 16 周 CP 小鼠的粪便明显不同（q<0.01）。用 Faith 的系统发育多样性测量的 α 多样性在健康对照的粪便中最低，在 16 周 CP 的粪便中最高（p<0.001）。使用线性判别分析检测到 CP 样本中差异富集的细菌分类群。双歧杆菌、阿克曼氏菌和脱硫弧菌属的细菌在 10 周 CP 小鼠的样本中富集。拟杆菌属、普雷沃氏菌属和拟杆菌属的细菌在 16 周 CP 小鼠的样本中富集。
综上所述，当小鼠发生 CP 时，肠道微生物组的组成、多样性和功能发生明显改变。
