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Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite significant advances in anti-infective, immunomodulatory, and organ function support technologies, the precise and targeted management of sepsis remains a challenge due to its high heterogeneity. Studies have identified disturbed tryptophan (TRP) metabolism as a common mechanism in multiple diseases, which is involved in both immune regulation and the development of multi-organ damages. The rise of research on intestinal microflora has further highlighted the critical role of microflora-regulated TRP metabolism in pathogen-host interactions and the "cross-talk" among multi-organs, making it a potential key target for precision medicine in sepsis. This article reviews TRP metabolism, the regulation of TRP metabolism by the intestinal microflora, and the characteristics of TRP metabolism in sepsis, providing clues for further clinical targeting of TRP metabolism for precision medicine in sepsis.
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Humanos , Microbioma Gastrointestinal/fisiología , Triptófano/metabolismo , Medicina de Precisión , SepsisRESUMEN
Objective:To investigate the dynamic changes of intestinal flora in septic model mice.Methods:Forty-two male SPF C57BL/6 mice were selected, the sepsis model was reproduced by cecal ligation and puncture (CLP), and the experimental mice were divided into CLP 6-12 hours group ( n = 9) and 1, 2, 3 days group (all n = 10) and Sham group ( n = 3) according to the time points after modeling. Intestinal flora 16S rRNA sequencing was carried out within feces from the colonic lumen of mice, and the effective sequences were clustered to obtain an operational classification unit (OTU) for statistical analysis of biological information, including Alpha diversity analysis, species composition analysis, principal coordinate analysis (PCoA analysis) and species difference analysis (LEfSe analysis), the dynamic changes of intestinal flora after CLP modeling were analyzed. Results:Compared with Sham group, with the prolongation of modeling time, the Alpha diversity of intestinal flora decreased, showing a decrease in community richness index (3 days after CLP: Chao index 1 was 367.9±162.6 vs. 508.3±105.9, Ace index was 372.5±151.9 vs. 498.8±104.2), Shannon index decreased in community diversity index (3 days after CLP: 2.57±1.06 vs. 4.30±0.57, Simpson index increased (3 days after CLP: 0.26±0.19 vs. 0.04±0.03), suggesting that with the progress of CLP modeling time, the richness and diversity of intestinal flora decreased. According to species composition analysis, in OTU level, OTU 633 accounted for the highest proportion in CLP 1 day group (24.79%), OTU 1016 was dominant in CLP 2 days and 3 days groups, and the highest proportion was 61.75% in CLP 3 days group; in genus level, the abundance of norank_f_Muribaculaceae showed a slight increase and then a significant decrease with time, the abundance of Escherichia-Shigella increased significantly in CLP 2 days and 3 days groups, the abundance of Lactobacillus increased first and then decreased with time, the abundance of Bacteroides showed a trend of gradual increase with time. PCoA analysis suggested that CLP 6-12 hours group had a higher structural similarity with Sham group. The flora structure changed gradually with the time after modeling, and the change was significant after 3 days of CLP. LEfSe analysis indicated that the main components that caused the differences among the groups were g _norank_f_Muribaculaceae, g _Prevotellaceae_UCG-001, s_uncultured_Bacteroidales_bacterium_g_norank_f_Muribaculaceae, g_Parabacteroides, Escherichia-Shigella and OTU 1016. The differences in abundance of Escherichia-Shigella and OTU 1016 among the five groups ranked first in the genus level and OTU level respectively; the abundance of Escherichia-Shigella gradually increased from 0.01% (0%, 0.02%) in 6-12 hours after CLP to 44.79% (3.71%, 53.75%) in 3 days with time, and the abundance of OTU 1016 increased from 0.01% (0%, 0.02%) in 6-12 hours after CLP to 44.69% (3.66%, 53.64%) in 3 days with time. Conclusion:Intestinal dysbiosis occurred in all CLP model groups, the diversity of the flora gradually decreased with the progress of modeling time, Escherichia-Shigella gradually became the dominant bacteria.
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Objective To assess the nutritional status of severe malnutrition patients with anorexia nervosa by multi-frequency bioelectrical impedance technique, and to provide the basis for nutritional support therapy. Methods A prospective study was conducted. Twenty-six severe malnutrition patients with anorexia nervosa, body mass index (BMI)≤16 kg/m2admitted to intensive care unit (ICU) of Peking University Third Hospital and general three ward of Peking University Sixth Hospital from June 1st to September 30th, 2017 were enrolled. The extracellular water (ECW), intracellular water (ICW), ECW/ICW ratio, adipose tissue mass (ATM), lean tissue mass (LTM), total body water/body weight (TBW/WT), ATM/WT, and LTM/WT were measured by multi-frequency bioelectrical impedance meter. Thirty-eighty healthy volunteers with normal nutritional status (23.0 kg/m2> BMI > 18.5 kg/m2) matched by gender and height were enrolled as healthy control group. The predictive value of main body composition for nutritional status were analyzed by receiver operating characteristic (ROC) curve. Results All the patients were female. There was no significant difference in height between two groups, but WT and BMI in the severe malnutrition group were significantly higher than those in the healthy control group [WT (kg): 38.1±4.9 vs. 54.2±3.3, BMI (kg/m2): 13.6±2.5 vs. 21.2±1.1, both 1 < 0.01]. Compared with the healthy control group, the ECW, ICW, ATM, LTM, ATM/WT and LTM/WT were significantly decreased in the severe malnutrition group [ECW (L): 9.02±0.42 vs. 10.19±0.77, ICW (L):12.6±0.9 vs.19.1±1.3, ATM (kg): 9.3±1.1 vs. 16.6±1.9, LTM (kg): 16.5±1.5 vs. 26.1±1.7, ATM/WT: 0.26±0.02 vs. 0.30±0.02, LTM/WT: 0.22±0.02 vs. 0.26±0.01, all 1 < 0.01], the ECW/ICW and TBW/WT were significantly increased in the severe malnutrition group (ECW/ICW: 0.72±0.06 vs. 0.54±0.06, TBW/WT: 0.58±0.02 vs. 0.52±0.02, both 1 < 0.01). It was shown by ROC curve analysis that the area under ROC curve (AUC) of TBW/WT、ATM/WT、LTM/WT for evaluating severe malnutrition were 0.999, 0.919, 0.954 respectively; when the cut-off of TBW/WT,ATM/WT, LTM/WT were 0.58, 0.28, 0.24 respectively, the sensitivity were 100%, 85%, 80% respectively, and the specificity were 95%, 80%, 91% respectively. Conclusion Main body composition of severe malnutrition patients with anorexia nervosa changed significantly. Bioelectrical impedance technology can be an effective assessment tool for the nutritional status of such patients.
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Antibiotics are the cornerstone to cure infectious diseases, however, it also destroys the intestinal inherent microflora, and may cause serious gastrointestinal dysfunction, such as abdominal distension, diarrhea, mucosal barrier damage etc. In severe conditions, it may induce intestinal sepsis. With the development of the human microbiology group program and the popularity of microbial sequencing technology, people can comprehend the effects of antibiotics on intestinal flora deeply, meanwhile the traditional biomedical model (the basis of bacterial disease) is questioned. It presents the effects and mechanisms of antibiotics on intestinal microflora and intestinal mucosal barrier function in detail and demonstrates the feasibility by the treatment of probiotics and fecal transplantation to construct "health-promoting microbes" to adjust gastrointestinal function, in addition, it can promote the rational use of antibiotics.
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Objective To estimate the prevalence and risk factors for irritable bowel syndrome (IBS) in China.Methods Cross-sectional studies relevant to IBS conducted among Chinese were identified through the databases including PubMed,Web of Science,the Cochrane Library,CBM,CNKI,Wanfang data and VIP.Quality of studies was assessed according to the criteria for cross-sectional studies recommended by Agency for Healthcare Research and Quality(AHRQ).Analysis of data,publication bias and sensitivity were performed with Stata (Version 12.0).Results A total of twenty-three studies were extracted.No obvious publication bias was detected in all analysis except the effect of depression on IBS prevalence.Pooled prevalence of IBS in China was 6.5％.IBS was more common in women than in men (8.1％ vs 6.8％;OR=1.23,95％CI 1.09-1.38) and high rate in age group between 30 to 59 years (6.9％ ; OR =1.22,95％ CI 1.12-1.32).Intestinal infection history(OR =2.39,95％ CI 1.69-3.38),anxiety (OR =2.95,95 ％ CI 1.94-4.49),depression (OR =1.85,95 ％ CI 1.11-3.09),food allergy (OR =2.80,95％ CI 2.12-3.67) and alcohol consumption (OR =1.15,95％ CI 1.07-1.24) might increase the risk for IBS.There were no significant difference of IBS prevalence between urban and rural areas (OR =0.97,95％ CI 0.72-1.29),neither in different education classes (OR =0.85,95％ CI 0.70-1.03).Sub-group analysis showed IBS prevalence varied apparently with different diagnostic criteria:prevalence defined by Manning was 11.8％ and by Rome Ⅱ and Rome Ⅲ prevalence values were 4.4％ and 8.9％ respectively.Conclusions Pooled prevalence of IBS in China was 6.5％.IBS is more common in age group between 30 to 59 years.Female,history of intestinal infection,anxiety,depression,food allergy and alcohol consumption were risk factors for IBS in Chinese population.