A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera Burkholderia-Caballeronia-Paraburkholderia, Faecalibacterium, and Ruminococcus_1 (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera Bacteroides, Muribaculaceae_unclassified, Muribaculum, and Alistipes) and eight enriched genera in the cholelithiasis group (genera Bifidobacterium, Streptococcus, Agathobacter, Ruminococcus_gnavus_group, Faecalibacterium, Subdoligranulum, Collinsella, Escherichia-Shigella) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera Burkholderia-Caballeronia-Paraburkholderia were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found via principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.

Editorial: The Microbiome in Hepatobiliary and Intestinal Disease

“…Gallbladder disease is linked to enriched Ruminococcus gnavus ( Wang et al, 2020a ; Zhang et al, 2021a ) and Akkermansia ( Liu et al, 2015 ; Zhang et al, 2021a ), and depleted Faecalibacterium ( Wu et al, 2013 ; Wang et al, 2020a ), Roseburia ( Wu et al, 2013 ; Keren et al, 2015 ; Zhang et al, 2021a ), and Prevotella 9 ( Wang et al, 2020a ; Zhang et al, 2021a ). Cholangiocarcinoma is associated with enlarged fecal proportions of Lactobacillus ( Jia et al, 2020 ; Zhang et al, 2021a ) and Peptostreptococcaceae ( Jia et al, 2020 ; Zhang et al, 2021a ), and smaller proportions of Ruminococcus ( Jia et al, 2020 ; Zhang et al, 2021a ) and Faecalibacterium ( Zhang et al, 2021a ).…”

“…Gallbladder disease is linked to enriched Ruminococcus gnavus ( Wang et al, 2020a ; Zhang et al, 2021a ) and Akkermansia ( Liu et al, 2015 ; Zhang et al, 2021a ), and depleted Faecalibacterium ( Wu et al, 2013 ; Wang et al, 2020a ), Roseburia ( Wu et al, 2013 ; Keren et al, 2015 ; Zhang et al, 2021a ), and Prevotella 9 ( Wang et al, 2020a ; Zhang et al, 2021a ). Cholangiocarcinoma is associated with enlarged fecal proportions of Lactobacillus ( Jia et al, 2020 ; Zhang et al, 2021a ) and Peptostreptococcaceae ( Jia et al, 2020 ; Zhang et al, 2021a ), and smaller proportions of Ruminococcus ( Jia et al, 2020 ; Zhang et al, 2021a ) and Faecalibacterium ( Zhang et al, 2021a ). The intestinal contributions of Streptococcus ( Wang et al, 2020b ; Song et al, 2021b ) and Klebsiella ( Wang et al, 2020b ; Song et al, 2021b ) are increased in biliary atresia, and those of Bifidobacterium ( Wang et al, 2020b ; Song et al, 2021b ), Blautia ( Wang et al, 2020b ; Song et al, 2021b ), and Faecalibacterium ( Wang et al, 2020b ; Song et al, 2021b ) are decreased.…”

Breast microbiome associations with breast tumor characteristics and neoadjuvant chemotherapy: A case-control study

“…In addition, Staphylococcal superantigens can induce the disturbance of the immune environment and upregulate the expression of CD25, FOXP3, and IL-17 and play a role in the pathogenesis of cutaneous lymphomas ( 33 ). In this study, we observed that the genus Burkholderia-Caballeronia-Paraburkholderia , which is positively associated with body mass index (BMI) ( 34 ), enriches in BC group. Obesity is well known as a typical risk factor for BC ( 35 , 36 ).…”

Codonopsis pilosula oligosaccharides modulate the gut microbiota and change serum metabolomic profiles in high-fat diet-induced obese mice

“…For example, the relative abundance of Rikenella was positively correlated with the weight of WAT, 46 and Burkholderia–Caballeronia–Paraburkholderi was shown to be positively correlated with the BMI. 47 Both Rikenella and Burkholderia–Caballeronia–Paraburkholderi were significantly decreased after CPO administration. Enterobacteriaceae spp.…”