Fibrosis F0-F1 (N= Fibrosis F2-4 (N= Microbial Species p value 33) % 16) % Unique Species in Stool Bacteroides 0.00 6.06 coprocola Coprococcus eutac-0.0012.12 tus Desulfovibrio piger 0.00 9.09 Desulfovibrio vul-0.003.03 garis Lactobacillus sali-0.006.06 varius Prevotella copri 0.00 3.03 Significantly Different Stool Species Peptostreptococcus 6.25 51

Background The role of gut microbiome in the pathogenic process of NAFLD has been increasingly recognized. However, the keystone species in the gut of NAFLD, the critical factor(s) in maintaining the stability of the entire gut microbiome, has not been reported. Method SparCC method was used to construct the microbial interaction ecosystem of human gut microbiome in healthy condition. PageRank algorithm was used to evaluate the importance of each bacterial species in healthy gut micro‐ecology system. Subsequently, the keystone species required for maintaining the stability of gut micro‐ecological system was identified on the basis of network stability assessment. Finally, the keystone species specific for NAFLD was determined by the quantitative analysis of gut microbiome between NAFLD patients and healthy people. And the relevant OTUs were annotated at species‐level based on phylogenetic trees. Furthermore, the same keystone species identification analysis was also conducted in NAFLD rats induced by high‐fat diet. Results Here we reconstructed the microbial interaction ecosystem of healthy human gut microbiome, consisting of 61 bacterial species and 90 pairwise interactions. Wherein, Bacteroides ovatus, Faecalibacterium prausnitzii, Barnesiella intestinihominis, Odoribacter splanchnicus , Roseburia faecis , Eubacterium ventriosum, Clostridium leptum were the seven keystone species that maintained the stability of the gut micro‐ecological system. The results of quantitative analysis indicated that the abundance of B. intestinihominis, E. ventriosum and C. leptum decreased significantly in the gut of NAFLD patients, and they were identified as the keystone species specific for NAFLD. These species could participate in the initiation and development of NAFLD by regulating the metabolic process of bile acid signaling and the activity of inflammasome. In addition, similar results were observed in the gut microbiome of NAFLD rats. Conclusion This research identifies the keystone species specific for NAFLD, and highlights a novel target for the precise prevention and treatment of NAFLD based on gut microbiome. Importantly, our strategy for the identification of the keystone species can be extended to other ecological systems. Support or Funding Information This work was supported by National Natural Science Foundation of China 81770571 (to LZ), 81774152(to RZ), 41530105 (to RZ). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

ETHNOPHARMACOLOGICAL RELEVANCE:Recipes (Qingre Jiedu (QJ), Wenyang Yiqi (WYYQ) and Huo Xue (HX)) in Qishen granules (QSG) are believed to synergistically exert cardio-protective effects. However, the underlying pattern of each decomposed recipe in QSG and their synergistic effects in the treatment of heart failure (HF) are not clear. OBJECTIVE:The purpose of this study is to explore the biological contributions of decomposed recipes to therapeutic effects of QSG and reveal the pharmacological mechanism of QSG in treating HF. MATERIALS AND METHODS:The therapeutic effects of QSG or its recipes on heart failure were examined in wet-lab at both transcription and phenotypic level using HF Sprague-Dawley rats. Sequencing and transcriptome analyses were performed using in silico approaches including identification of differentially expressed genes, pathway enrichment and protein-protein interaction network studies. Specially, an optimized in silico quantitative pathway analysis that maximally extracted gene expression information was developed to reveal differentially expressed pathways (DEPs) among various groups, and is publicly available as R package QPA on GitHub (https://github.com/github-gs/QPA). Finally, the HF-related genes predicted using DEP approach were validated by quantitative real-time polymerase chain reaction and western blot. RESULTS:Multiple key genes and the associated signaling pathways were shown to be highly relevant for the therapeutic effect of QSG. Decreased expression of Spp1 gene required for inflammatory signaling and profibrotic signaling were observed in failing hearts treated with QJ, WYYQ and HX. Decreased expression of Cx3cr1 gene required for inflammatory signaling was observed in failing hearts treated with WYYQ and HX. Decreased expression of Myc gene required for oxidative stress and Fgfr2 gene required for profibrotic signaling were observed in failing hearts treated with HX and WYYQ, respectively. Increased expression of Adcy1 gene required for cAMP-PKA signaling cascade was observed in failing hearts treated with WYYQ and HX. CONCLUSIONS:Our study suggests that QJ, WYYQ and HX recipes in QSG achieve synergistic and complementary therapeutic effects through alleviating inflammatory responses, attenuating ventricular remodeling and enhancing myocardial energy supply.

BACKGROUND Ulcerative colitis (UC) is considered to be closely associated with alteration of intestinal microorganisms. According to the traditional Chinese medicine (TCM) theory, UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun (PXSY) and Da-Chang-Shi-Re (DCSR). The relationships among gut microbiota, TCM syndromes, and UC pathogenesis have not been well investigated. AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes. METHODS From May 2015 to February 2016, UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. Fresh stool specimens of UC patients with PXSY or DCSR were collected. The feces of the control group came from the health examination population of Longhua Hospital. The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA. The high-throughput sequencing reads were processed with QIIME, and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS The composition of gut bacterial communities in 93 stool samples (30 healthy controls, 32 patients with PXSY syndrome, and 31 patients with DCSR syndrome) was determined by the pyrosequencing of 16S ribosomal RNA. Beta diversity showed that the composition of the microbiota was different among the three groups. At the family level, Porphyromonadaceae, Rikeneliaceae, and Lachnospiraceae significantly decreased while Enterococcus, Streptococcus, and other potential pathogens significantly increased in UC patients compared to healthy subjects. At the genus level, Parabacteroides, Dorea, and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls. Five differential taxa were identified between PXSY and DCSR syndromes. At the genus level, a significantly increased abundance of Streptococcus was observed in DCSR patients, while Lachnoclostridium increased in PXSY patients. The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism, immunity, and the metabolism of polypeptides. CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.