Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.

The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.

Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis.

INTRODUCTION: Infected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. METHODS: Patients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1ß, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. RESULTS: We recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5-97.4) in discriminating IPN. CONCLUSION: HLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.