Exploring on Mechanism of Gegen Qinliantang in Interventing Antibiotic-associated Diarrhea Based on 16S rRNA Sequencing and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg-1） as well as Lizhu Changle group（0.15 g·kg-1）， except for the blank group， each group was given clindamycin（250 mg·kg-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Probiotics for the Prevention of Antibiotic-Associated Diarrhea.

Several communities have started using probiotic-rich fermented foods as therapeutic options with presumed medicinal powers. We now know the importance of microbiome balance and how probiotics can restore imbalances in the microbiome. Probiotics have been tested for a number of clinical uses such as the prevention of antibiotic-associated diarrhea (AAD), the treatment of various diseases such as H. pylori infection, irritable bowel disease, vaginitis, the prevention of allergies, and necrotizing enterocolitis in newborns. AAD has been the most indicated therapeutic use for probiotics. AAD is a common side effect of antibiotic usage, which affects up to 30% of patients. The hypothesis behind using probiotics for AAD is that they help normalize an unbalanced flora. There are many potential mechanisms by which probiotics support intestinal health such as (i) boosting immunity, (ii) increasing gut barrier integrity, (iii) producing antimicrobial substances, (iv) modulating the gut microbiome, (v) increasing water absorption, and (vi) decreasing opportunistic pathogens. Many randomized-controlled trials including the strain-specific trials that use Lactobacillus and Saccharomyces and meta-analyses have shown the benefits of probiotics in addressing AAD. Although adverse events have been reported for probiotics, these are broadly considered to be a safe and inexpensive preventative treatment option for AAD and other gastrointestinal disorders.

Clinical characteristics and factors related to antibiotic-associated diarrhea in elderly patients with pneumonia: a retrospective cohort study.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a common problem among elderly inpatients because many elderly patients are admitted for pneumonia or other conditions that necessitate antibiotic treatment. In the super aging population, more patients are suffering from pneumonia than before, but the incidence or risk factors for AAD among many elderly patients have not been well scrutinized. METHODS: We conducted a retrospective cohort study of elderly patients diagnosed with pneumonia from April 2014 to March 2019 who were admitted to the Department of General Medicine of a Tertiary Care Hospital in Japan. Patients (≥ 65 years of age) who were diagnosed with bacterial pneumonia or aspiration pneumonia and treated with antibiotics were included. We defined AAD by diarrhea with more than three loose or watery stools per day and included patients who had these symptoms for either one day or two or more consecutive days. We also assessed the length of hospital stay and in-hospital mortality. The potential risk factors for AAD included age, sex, body weight, body mass index, smoking, alcohol, activities of daily living (ADL),　comorbidities, vital signs, laboratories, the severity of pneumonia, antibiotic and other medication use. RESULTS: There were 1,067 patients, the mean age was 83 years, and men accounted for 59 %. ß-Lactamase inhibitors were frequently prescribed antibiotics in 703 patients (66 %), and proton pump inhibitors (PPIs) were also commonly administered (48 %). AAD developed in 322 patients (30 %). The multivariate logistic regression model showed that ß-lactamase inhibitors (OR 1.43, 95 % CI 1.05-1.95) and PPIs (OR 1.37, 95 % CI 1.03-1.83) were associated with AAD as well as age (OR 1.03 per year, 95 % CI 1.01-1.05). CONCLUSIONS: AAD was common among elderly inpatients with pneumonia, and ß-lactamase inhibitors and PPIs were associated with AAD. Strict use of such medication should be considered to decrease the risk of AAD.

Antibiotics as Major Disruptors of Gut Microbiota.

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system. Antibiotic use can have several negative effects on the gut microbiota, including reduced species diversity, altered metabolic activity, and the selection of antibiotic-resistant organisms, which in turn can lead to antibiotic-associated diarrhea and recurrent Clostridioides difficile infections. There is also evidence that early childhood exposure to antibiotics can lead to several gastrointestinal, immunologic, and neurocognitive conditions. The increase in the use of antibiotics in recent years suggests that these problems are likely to become more acute or more prevalent in the future. Continued research into the structure and function of the gut microbiota is required to address this challenge.

A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in The Netherlands.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a side-effect frequently associated with the use of broad spectrum antibiotics. Although a number of clinical studies show that co-administration of specific probiotics reduces the risk for AAD, there is still unclarity among healthcare professionals on the recommendation of probiotic products. This paper aims at a practical guide to inform healthcare professionals, patients and consumers about the exact product characteristics of available probiotics with a proven efficacy to prevent AAD. METHODS: The workflow in this paper includes three consecutive steps: 1) systematic review of relevant clinical studies for effective probiotics by a meta-analysis, 2) compilation of a list of available probiotic products, and 3) recommendation of probiotic products that match effective formulations. Our systematic review on the efficacy of probiotics for the prevention of AAD included only studies with randomized, double blind placebo-controlled trials, a clear definition of antibiotic associated diarrhea, and a probiotic administration regime for at least the duration of the antibiotic therapy. RESULTS: Using our inclusion criteria, we selected 32 out of 128 identified trials and pooled the results of these studies for each specific dairy product and food supplement. The results indicate a total of seven single or multiple-strain formulations favoring the probiotic treatment group, with the strain Lactobacillus rhamnosus GG being the most effective [relative risk ratio of probiotic versus placebo 0.30 (95% CI 0.16-0.5)]. We selected products for recommendation from a compiled list of all probiotic dairy products and food supplements available in The Netherlands and categorized them into groups of products showing effects against the incidence of AAD in at least one, two or three independent clinical studies. We excluded all products which did not unambiguously declare on the label the specific probiotic strain(s) and the number of colony forming units. CONCLUSION: Here we present a practical guide that informs healthcare professionals and patients on the availability of probiotic products with a proven efficacy for the prevention of AAD.

Incidence and Outbreak of Healthcare-Onset Healthcare-Associated Clostridioides difficile Infections Among Intensive Care Patients in a Large Teaching Hospital in China.

Background:Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality among hospitalized patients. In China, however, hospital staff do not routinely test for CDI, leading to under-diagnosis and poor patient outcomes. Locally generated CDI data can help assess the magnitude of the problem and strengthen approaches for CDI prevention and control. Methods: We prospectively monitored hospital-onset hospital-associated (HOHA) CDI in four intensive care units (ICUs) from June 2013 to September 2014 in a large teaching hospital in China. We collected clinical information from all ICU patients with ≥ 3 episodes of diarrhea occurring within a 24-h period at least 48 h following admission (suspect case definition). Stool specimens were collected from all suspect cases of CDI and cultured for C. difficile. Polymerase chain reaction (PCR) was used to detect toxin genes from positive isolates; multi-locus sequence typing (MLST) was used for typing and identifying novel strains. We estimated the incidence rate as the number of HOHA CDI cases per 10,000 patient days; 95% confidence intervals were generated to assess rate differences between the four ICUs. Results: A total of 593 hospital-onset diarrhea patients met the suspect case definition during the study period. Of these, 47 patients (8%) were positive for C. difficile and toxin genes. The HOHA-CDI incidence rate was 14.1 cases per 10,000 patient days (95% CI: 10.5-18.6). Six patients with HOHA CDI died. ST54 (n = 14, 20%) was the most common type of HOHA-CDI strain circulating in the hospital during the study period and was linked to a temporal cluster (outbreak) involving two (NICU and GICU) of the four ICUs. Conclusion: HOHA-CDI occurs among ICU patients at this teaching hospital, supporting the importance of routine testing for CDI. Information on strain distribution can help detect CDI outbreaks. Detection of ST54 strain in a temporal cluster suggests possible gaps in infection control practices that should be investigated and addressed as needed.

Microeological Modulator in Preventing Neonatal Antibiotic Associated Diarrhea:A Clinical Research / 中华医院感染学杂志

OBJECTIVE To understand the clinical effect of microeclogical modulator Bifid Triple Viable(BTV) in preventing neonatal antibiotic associated diarrhea(AAD).METHODS A prospective controlled study was undertaken on the antibiotic treated group and control group from Jan,2004 to Dec 2007.RESULTS Among the 996 neonatal patients in treated group,71 patients occurred AAD,with the morbidity of 7.13%.Among the 1012 neonatal patients in control group,235 patients occurred AAD(morbidity 23.22%).There was significant difference between the two groups(P