A large number of previous studies have confirmed that there are different degrees of alteration of gut microbiota in all kinds of chronic liver diseases, and the changes of the gut microbiota play an important role in the occurrence and development of chronic liver disease.25 Moreover, treating a disease or improving its prognosis can be achieved by regulating the gut microbiota. Some studies have shown that partial beneficial bacteria may play a role in the immune clearance of viruses in young HBV infected persons. Another study found that the fecal bacteria transplantation in CHB patients with HBeAg positive was more likely to produce HBeAg seroconversion than patients with oral antiviral drugs alone. 26 In addition,The regulatory effect of traditional Chinese medicine on gut microbiota has always been concerned. Ever-increasing evidence suggests that gut microbiota plays a crucial role in Herbal medicine therapy by complicated interplay with Herbal medicine components.27 It is of great significance to study the biological basis of TCM syndrome based on gut microbiota to guide the syndrome differentiation and treatment of CHB.
In this study, the TCM Syndromes of 116 patients with CHB showed damp heat syndrome in 65 cases (56.03%), liver depressione and spleen deficiency syndrome in 28 cases (24.14%), blood stasis syndrome in 10 cases (8.62%), Yin deficiency of liver and kidney syndrome in 9 cases (7.76%), and Yang deficiency of spleen and kidney in 4 cases (3.45%),which further confirmed that damp heat syndrome and liver depressione and spleen deficiency syndrome were the main TCM Syndromes of CHB. It should be noted that damp heat syndrome was the most common TCM syndromes in CHB patients,which might be related to the theory of traditional Chinese medicine that damp heat was the basic pathological factor of CHB.28 Except for the slightly different GGT changes, there was no significant difference in ALT, AST, and HBV DNA etc major laboratory diagnostic indexes between damp heat syndrome and liver depressione and spleen deficiency syndrome( P > 0.05).Therefore, it was necessary to explore the biological indicators that can further reflect the scientific connotation of these two syndromes.
The analysis of Venn diagram of gut microbiota showed that there was a large number of the same OTUs in the two TCM syndrome groups, and there were also specific OTUs in each group.In PLS-DA analysis, the flora composition of the two groups was clearly separated, and there were overlaps in the middle. All of these indicated that there were differences in the gut microbiota of CHB patients with damp heat syndrome and liver depression and spleen deficiency syndrome, but the differences could not be completely distinguished.Why did this happen?The possible explanation was as follows:According to the theory of TCM,damp heat is the basic pathological factors of CHB, which can run through the whole course of the disease.Therefore, the liver depression and spleen deficiency syndrome can not only contain the syndrome factors of damp heat syndrome in part,but also can but also can transform from liver depression and spleen deficiency to damp heat,due to spleen deficiency can't transport and change water dampness with a result that a prolonged water dampness will accumulated into damp heat.28
Based on the analysis of relative abundance of gut microbiota at the level of phylum, class, order, family and genus, it showed that only Cyanobacteria at the level of phylum was found in the damp heat syndrome of CHB patients.Cyanobacteria may produce microcystin which can cause liver damage and necrosis, even induce the occurrence of liver cancer. In addition, it may also have a significant inhibitory effect on immune function.29,30 Sowe should pay attention to the role of Cyanobacteria in the occurrence and development of damp heat syndrome in CHB patients.In addition, the relative abundance of Subdiligranulum was lower in liver depression and spleen deficiency syndrome in our study.It had been found that the abundance of Subdiligranulum in the HBV decompensate cirrhosis patients was significantly lower than that in the healthy people.31 Whether "liver depression and spleen deficiency syndrome of CHB - Subdiligranulum - decompensation of HBV related cirrhosis " has a certain inevitable relationship needs further study.
Furthermore, the relative abundance of Erysipelotrichia and Erysipelotrichaceae were higher in liver depression and spleen deficiency syndrome.Previous studies had shown that erysipelas were not only positively correlated with fatty liver,32 but also strongly correlated with diabetic nephropath.33 Subdoligranulum,as a biomarker in liver depression and spleen deficiency syndrome,the changes of its abundance will lead to metabolic disorders of the host. 34 In addition, this part of research showed that the number of Subdolegranulum in patients with ulcerative colitis was higher than that in healthy people. Therefore, Subdoligranulum may be related to the intestinal inflammation. The intestinal inflammation, intestinal mucosal barrier damage, harmful intestinal bacteria and their metabolites enter the liver through the portal vein, and then promote the liver inflammation or aggravate the liver inflammation.35 Therefore, CHB patients with liver depression and spleen deficiency syndrome may be more likely to develop fatty liver, diabetes and other metabolic diseases than those with damp heat syndrome. This study only conducted a preliminary study on the characteristics of gut microbiota of the two most common TCM syndromes in patients with CHB, the sample size was not large enough and the study of metabolites and related metabonomics of gut microbiota was still blank. In particular, the interpretation of the biological significance of related gut microbiota in TCM needs to be further studied.