Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition

Abstract

Purpose Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota. Design Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry. Results Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines. Conclusion These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.

Global Host Responses to the Microbiota at Single Cell Resolution in Gnotobiotic Zebrafish

“…The exocrine pancreas produces digestive enzymes that are packaged into vesicle-granules and delivered into the intestinal lumen by secretion. GO analysis indicated that the microbiota stimulates a diversity of biological processes in exocrine pancreas acinar cells including secretory vesicle formation, transporter activity, and regulation of catabolism, consistent with several studies showing associations between exocrine pancreas function and microbiota composition (Nishiyama et al ., 2018; Adolph et al ., 2019; Frost et al ., 2019; Pietzner et al ., 2021). Pancreatic acinar cells are not only responsible for organ function but also for organ development (Biemar et al ., 2001; Field et al ., 2003; Wan et al ., 2006).…”

A Pilot Study of the Effect of Lactobacillus casei Obtained from Long-Lived Elderly on Blood Biochemical, Oxidative, and Inflammatory Markers, and on Gut Microbiota in Young Volunteers

“…Previous studies have shown that by regulating the intestinal flora, the host's capacity to resist pathogens can be improved, thereby strengthening the intestinal structure and immune system [12], and alleviating chronic inflammation [13]. Furthermore, intestinal flora shows evidence of plasma metabolism regulation [14] and healthy intestinal flora helps regulate cholesterol homeostasis and prevent or treat vascular disease [15]. Studies have proved that the intestinal flora controls type 2 immunity by inducing type T cells, balancing immune responses at the mucosal surface [16].…”

Chronic pancreatitis and the intestinal microbiome in adults and children: Not only SIBO but also gut dysbiosis has clinical significance

“…Значимое увеличение относительной численности Prevotella, связанной с развитием хронического воспаления, может способствовать дальнейшему снижению внешнесекреторной функции поджелудочной железы, а потеря «филогенетического разнообразия», в свою очередь, может снизить сопротивляемость организма к желудочно-кишечным инфекциям [12]. Кроме того, экзокринная недостаточность поджелудочной железы при хроническом панкреатите может влиять на состав и уровень микробных метаболитов в крови, напрямую способствуя развитию метаболических изменений в организме [8,13].…”