Barko Patrick C, Rubin Stanley I, Swanson Kelly S, McMichael Maureen A, Ridgway Marcella D, Williams David A
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Animals (Basel). 2023 Jul 14;13(14):2313. doi: 10.3390/ani13142313.
Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome resulting from insufficient secretion of pancreatic digestive enzymes. EPI is treated with pancreatic enzyme replacement therapy (PERT), but the persistence of clinical signs, especially diarrhea, is common after treatment. We used untargeted metabolomics of serum to identify metabolic disturbances associated with EPI and generate novel hypotheses related to its pathophysiology. Fasted serum samples were collected from dogs with EPI ( = 20) and healthy controls ( = 10), all receiving PERT. Serum metabolomes were generated using UPLC-MS/MS, and differences in relative metabolite abundances were compared between the groups. Of the 759 serum metabolites detected, 114 varied significantly ( < 0.05, q < 0.2) between dogs with EPI and healthy controls. Differences in amino acids (arginate, homoarginine, 2-oxoarginine, N-acetyl-cadaverine, and α-ketoglutaramate) and lipids (free fatty acids and docosahexaenoylcarnitine) were consistent with increased proteolysis and lipolysis, indicating a persistent catabolic state in dogs with EPI. Relative abundances of gut microbial metabolites (phenyllactate, 4-hydroxyphenylacetate, phenylacetyl-amino acids, catechol sulfates, and o-cresol-sulfate) were altered in dogs with EPI, consistent with disruptions in gut microbial communities. Increased kynurenine is consistent with the presence of intestinal inflammation in dogs with EPI. Whether these metabolic disturbances participate in the pathophysiology of EPI or contribute to the persistence of clinical signs after treatment is unknown, but they are targets for future investigations.
外分泌性胰腺功能不全（EPI）是一种由于胰腺消化酶分泌不足导致的吸收不良综合征。EPI采用胰酶替代疗法（PERT）进行治疗，但治疗后临床症状持续存在，尤其是腹泻，这很常见。我们利用血清的非靶向代谢组学来识别与EPI相关的代谢紊乱，并生成与其病理生理学相关的新假设。从患有EPI的犬只（n = 20）和健康对照犬只（n = 10）中采集空腹血清样本，所有犬只均接受PERT。使用超高效液相色谱-串联质谱法（UPLC-MS/MS）生成血清代谢组，并比较两组之间相对代谢物丰度的差异。在检测到的759种血清代谢物中，114种在患有EPI的犬只和健康对照犬只之间存在显著差异（P < 0.05，q < 0.2）。氨基酸（精氨酸盐、高精氨酸、2-氧代精氨酸、N-乙酰尸胺和α-酮戊二酸）和脂质（游离脂肪酸和二十二碳六烯酰肉碱）的差异与蛋白水解和脂肪分解增加一致，表明患有EPI的犬只存在持续的分解代谢状态。患有EPI的犬只肠道微生物代谢物（苯乳酸、4-羟基苯乙酸、苯乙酰氨基酸、儿茶酚硫酸盐和邻甲酚硫酸盐）的相对丰度发生改变，这与肠道微生物群落的破坏一致。犬尿氨酸增加与患有EPI的犬只存在肠道炎症一致。这些代谢紊乱是否参与EPI的病理生理学过程或导致治疗后临床症状的持续存在尚不清楚，但它们是未来研究的目标。
