The Correlation Between Intestinal Mucosal Barrier Impairment And Depressive Disorder In Patients With Colon Cancer

The current pathogenesis of depressive disorder is not entirely clear,mainly related to the emotional central neurotransmitters(such as serotonin,etc.)disorder.The incidence of depressive disorder in colon cancer patients is increasing,and the specific mechanism is not clear.More and more studies have shown that intestinal flora can have important effects on host behavior,such as stress response,anxiety and depressive disorder,through the gut-brain axis.Animal studies have shown that gut microbiota-derived metabolites can act on intestinal chromaffin cells(ECs)and regulate the release of 5-HT.Objective To investigate the correlation between intestinal mucosal barrier impairment and depressive disorder in patients with colon cancer before operation,through the study of the occurrence of depressive disorder in colon cancer patients.Methods All of the consecutive patients with primary colon cancer admitted to our hospital for surgical treatment were prospectively considered from June 2015 to December 2016.The screening,diagnosis and evaluation of depressive disorder were followed by the revision of the ACOS and the Hamilton Depression Scale-24(HAMD-24)and were eventually assessed by two senior medical psychologists.Polymerase chain reaction was used to detect bacterial DNA in the peripheral blood of colon cancer patients.The concentration of serotonin(5-HT)in plasma was detected by enzyme-linked immunosorbent assays,and 5-HT-specific staining was used to observe the number of 5-HT-positive enterochromaffin cells(ECs).Western blotting and immunohistochemistry was used to detect the levels of the expression of tight junction(TJ)proteins occluding(OC),claudins-1(CL-1),and Zonula occluden-1(ZO-1).16 Sr RNA gene Illumina sequencing,454 pyrosequencing,and denaturing gradient gel electrophoresis(DGGE)were used to analyze the intestinal microbial community structure of the colon cancer patients with depressive disorder and the colon cancer patients without depressive disorder.Results According to the selection and exclusion criteria,84 patients with colon cancer were eligible for inclusion in the study,including 28 colon cancer patients with depressive disorder and 56 non-depressive disorder colon cancer patients.The BT ratio in colon cancer patients with depressive disorder(9/28,32.1%)was significant higher than in non-depressive disorder colon cancer patients(7/56,12.5%,p=0.031).Patients with depressive disorder had a lower blood level of serotonin than patients with non-depressive disorder(86.22ng/m L vs.116.46ng/m L,p<0.0001),and had fewer 5-HT-positive cells per area of colonic epithelial tissue(p<0.0001).Depressive disorder patients had lower levels of CL-1(p=0.015),OC(p=0.018),ZO-1(p=0.01)than patients with non-depressive disorder.Compared to patients without depressive disorder,depressive disorder patients had a higher relative abundance of Bacteroidetes(6.6% vs.1.8%,p<0.001),Alistipes(3.5% vs.1%,p<0.001),Enterobacteriaceae(1.4% vs.1%,p<0.001),Fusobacteriaceae(1.8% vs.1%,p<0.001),and Acidaminococcaceae(4% vs.2.2%,p<0.001).In contrast,patients with depressive disorder had a significantly lower abundance of Lactobalillus(10.2% vs.12.4%,p<0.001),Bifidobacterium(10.2% vs.11.5%,p<0.001),Faecalibacterium(0.6% vs.1.1%,p<0.001),and Bacteroidaceae(42.4% vs.44%,p<0.001).Conclusions The impairment of the intestinal mucosal barrier in colon cancer patients may contribute to the development of depressive disorder and may be related to the reduction of 5-HT secretion resulting from alterations in gut microbiota.