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The human gut microbiome is acknowledged as being associated with homeostasis and the pathogenesis of several diseases. Conventional culture techniques are limited in that they cannot culture the commensals; however, next-generation sequencing has facilitated the discovery of the diverse and delicate microbial relationship in body sites and blood. Increasing evidence regarding the blood microbiome has revolutionized the concept of sterility and germ theory in circulation. Among the types of microbial communities in the blood, bacteriomes associated with many health conditions have been thoroughly investigated. Blood bacterial profiles in healthy subjects are identified as the eubiotic blood bacteriome, whereas the dysbiotic blood bacteriome represents the change in bacterial characteristics in subjects with diseases showing deviations from the eubiotic profiles. The blood bacterial characteristics in each study are heterogeneous; thus, the association between eubiotic and dysbiotic blood bacteriomes and health and disease is still debatable. Thereby, this review aims to summarize and discuss the evidence concerning eubiotic and dysbiotic blood bacteriomes characterized by next-generation sequencing in human studies. Knowledge pertaining to the blood bacteriome will transform the concepts around health and disease in humans, facilitating clinical implementation in the near future.

Background Lifestyle modification, including dietary intervention or exercise training, has beneficial effects on the improvement of metabolic and brain function in cases of metabolic syndrome, diabetes and Alzheimer’s disease. However, the comparative effects of calorie restriction, exercise training, and a combination of calorie restriction and exercise training on brain and cognitive function in the obese condition have not been thoroughly investigated. Our hypothesis is that both calorie restriction and exercise training improve brain and cognitive function in an obese condition, but a combination of these two therapies has a greater efficacy in the restoration of brain functions and cognition than either single therapy. Method Twenty‐five female rats were fed with either a normal diet (ND; n=5) or a high‐fat diet (HFD; n=20) for 27 weeks. At week 20, the ND‐fed rats were assigned to a sedentary lifestyle (NDS; n=5), and HFD‐fed rats were assigned to either a sedentary lifestyle (HFS; n=5), calorie restriction (HFCR; n=5), exercise (HFEX; n=5) or a combination of calorie restriction and exercise (HFCB; n=5) for 7 weeks. After that, metabolic parameters, brain parameters and cognition were determined. Result HFD‐fed rats developed insulin resistance and cognitive decline via increased oxidative stress, inflammation, apoptosis, and synaptic dysfunction in the hippocampus. Calorie restriction decreased metabolic disturbance, decreased inflammation and oxidative stress in the hippocampus, but failed to improve cognition in HFD‐fed rats. Exercise attenuated metabolic disorders, oxidative stress, inflammation, apoptosis, and synaptic dysfunction, resulting in improved cognition in HFD‐fed rats, while the combined therapy had the greatest beneficial effect on this improvement (p<0.05, Figure 1). Conclusion A combination of calorie restriction and exercise may be the best therapeutic approach for the restoration of brain and cognitive function in the obese condition.

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BackgroundDonepezil (DPZ) is an acetylcholinesterase inhibitor used to improve cognitive function. We reported that it prevented doxorubicin (Dox)‐induced chemobrain. Gut epithelial disruption, gut dysbiosis and impaired essential microbial metabolites, such as short chain fatty acids (SCFAs), have found following Dox therapy. However, the impact of DPZ to prevent gut epithelial disruption and gut dysbiosis as well as disturbance of circulating SCFAs due to Dox‐induced chemobrain have been never investigated.MethodTwenty‐four rats were divided into sham rats, vehicle‐treated Dox rats, and DPZ‐treated Dox rats. Modified Novel Object Location and Recognition tests were used to evaluate cognitive function. At the end of the study, ileums were removed to investigate occludin protein expression, and PCR of ileal luminal contents were used to calculate Firmicutes to Bacteroidetes (F/B) ratio. Serum butyric acid, a representative of SCFAs, was assessed by Gas chromatography‐mass spectrometry.ResultDox‐rats developed cognitive impairment with gut epithelial disruption, gut dysbiosis and reduced essential microbial metabolites (serum butyric acid). DPZ significantly prevented cognitive decline in Dox‐rats (Fig 1A‐C). Furthermore, DPZ restored the expression of occludin in gut tissue, suggesting that DZP improved gut epithelial integrity in Dox‐rats (Fig 1D). DZP improved gut dysbiosis in Dox‐rats as indicated by attenuated F/B ratio (Fig 1E), but level of serum butyric acid between DZP‐treated Dox rats and vehicle‐treated Dox rats was not different (Fig 1F).ConclusionDPZ co‐treatment with Dox prevented Dox‐induced cognitive impairment. Although DZP protected gut epithelial disruption, and improved gut dysbiosis, however it could not help to increase circulating SCFAs. These findings suggest that DPZ, itself, cannot completely prevent the gut disturbance in rats with Dox‐induced chemobrain. Therefore, the probiotic supplement with DZP might be the other approach to prevent gut problem following chemotherapy.

4104 Background: Gut microbiota established crucial roles in host metabolism and several diseases, particularly cancers. Distinct bacterial profiles from intestine are found to be a potential factor in carcinogenesis, while some of those are associated with detrimental treatment to the responsiveness in various types of cancer. Association of gut microbiota and treatment outcome has been thoroughly investigated in intrahepatic cholangiocarcinoma (ICCA). The present study aimed to compare gut microbiota profiles between chemotherapy responder and non-responder in ICCA patients. Methods: Unresectable or metastatic ICCA patients were recruited in the study. The criteria of all patients were naïve to chemotherapy. All patients received first line combination of cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 at day1 and day 8 in every 21-day cycle and were given up to 8 cycles. The primary endpoint was to evaluate the association between gut microbiota and the objective response rate. Bacterial genomic DNA samples were extracted from the stool using a commercial genomic DNA isolation kit (Qiagen, Hilden, Germany) and then underwent next-generation sequencing. Data analyses were conducted by using QIIME2 and Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC). Results: Seventeen ICCA patients were recruited. The objective response rate was 23.5% comparable to historical study. Chemotherapy responder group was defined as partial response patients (N = 4) and chemotherapy non-responder group included stable of disease and progressive disease (N = 13). Baseline characteristics were similar including age, sex, ECOG performance status, numbers of metastatic organ and CA 19-9 in two groups. Median Age were 63 years old (60-70) and 61 (45-73), respectively. Alpha-diversity and beta-diversity were not different between two groups. In chemotherapy non-responder group, some taxa were dominantly observed including Ruminococcaceae, Oribacterium, Oxalobacter, Peptostreptococcus, Aggregabacter, which had been previously reported increasing in ICCA patients. Interestingly, Ruminococcaceae, which was previously documented to be correlated with vascular invasion, was significantly increased abundance in non-responder group. Moreover, the median progression-free survival (PFS) was improved in chemotherapy responder group compared to non-responder group 11.8 and 6.6 month, respectively. Large sample sizes study to confirm this study result should be developed. Conclusions: Distinct bacteria from gut microbiota such as Ruminococcaceae has inversely associated with chemotherapy response in ICCA patients receiving first line cisplatin and gemcitabine combination, suggesting the possibility of the poorer PFS.