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Human intestinal microbiota gene risk factors for antibiotic-associated diarrhea: perspectives for prevention. Risk factors for antibiotic-associated diarrhea.

ABSTRACT: Antibiotic-associated diarrhea (AAD) is associated with altered intestinal microflora and other symptoms that may lead to possibly death. In critically ill patients, diarrhea increases rates of morbimortality. Assessing diarrhea risks is thus important for clinicians. For this reason, we conducted a hypothesis-generating study focused on AAD to provide insight into methods of prevention. We evaluated the hypothesis of predisposing factors within the resident intestinal microbiota in a cohort of outpatients receiving antibiotherapy. Among the pool of tested variables, only those related to bacterial 16S rRNA genes were found to be relevant. Complex statistical analyses provided further information: amid the bacteria 16S rRNA genes, eight were determined to be essential for diarrhea predisposition and characterized from the most important to the least. Using these markers, AAD risk could be estimated with an error of 2%. This molecular analysis offers new perspectives for clinical applications at the level of prevention.

SUBMITTER: de La Cochetiere MF

PROVIDER: S-EPMC3348119 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Human intestinal microbiota gene risk factors for antibiotic-associated diarrhea: perspectives for prevention. Risk factors for antibiotic-associated diarrhea.

de La Cochetière Marie-France MF Montassier Emmanuel E Hardouin Jean-Benoit JB Carton Thomas T Le Vacon Françoise F Durand Tony T Lalande Valerie V Petit Jean Claude JC Potel Gilles G Beaugerie Laurent L

Microbial ecology 20100226 4

Antibiotic-associated diarrhea (AAD) is associated with altered intestinal microflora and other symptoms that may lead to possibly death. In critically ill patients, diarrhea increases rates of morbimortality. Assessing diarrhea risks is thus important for clinicians. For this reason, we conducted a hypothesis-generating study focused on AAD to provide insight into methods of prevention. We evaluated the hypothesis of predisposing factors within the resident intestinal microbiota in a cohort of ...[more]

PMID: 20186408

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Project description:Diarrhea is one of the common adverse reactions in antibiotic treatment, which is usually caused by the imbalance of intestinal flora, and probiotics play an important role in the structure of intestinal flora. Therefore, this experiment studied the regulatory effect of Lactiplantibacillus plantarum 2-33 on antibiotic-associated diarrhea (AAD) mice. First, the AAD mice model was established by the mixed antibiotic solution of gentamicin sulfate and cefradine. Then, the physiological indexes and diarrhea of mice were observed and recorded by gastric perfusion of low dose (1.0 × 107 CFU/ml), medium dose (1.0 × 108CFU/ml), and high dose (1.0 × 109 CFU/ml) strain 2-33. 16S rRNA gene V3-V4 regions were sequenced in colon contents of mice in control group, model group, self-healing group, and experimental group, respectively, and the diversity of intestinal flora and gene function prediction were analyzed. The results showed that the intestinal flora of AAD mice was not significantly regulated by gastric perfusion of strain 2-33 to 7 days, but the relative abundance and diversity of intestinal flora of AAD mice were significantly improved by gastric perfusion to 14 days (p < 0.05). In addition, at the genus level, the relative abundance of Lactobacillus increased significantly, and the relative abundance of Enterococcus and Bacillus decreased significantly (p < 0.05). In addition, the regulation of strain 2-33 on intestinal flora of AAD mice was time- and dose-dependent, short-term gastric perfusion, and low dose had no significant effect (p > 0.05). Strain 2-33 can significantly increase the levels of anti-inflammatory cytokines IL-4 and IL-10, significantly decrease the levels of proinflammatory cytokines TNF-α and IFN-γ (p < 0.05), and can also adjust carbohydrate metabolism, amino acid metabolism, and energy metabolism to normal levels, thus accelerating the recovery of intestinal flora structure of AAD mice. In summary, strain 2-33 can improve the structure and diversity of intestinal flora of AAD mice, balance the level of substance and energy metabolism, and play a positive role in relieving diarrhea, maintaining and improving the intestinal microecological balance.

Project description:In recent years, sweeteners have gained massive popularity under the trend of limiting sugar intake. Our previous study found that Qiweibaizhu Powder (QWBZP) could improve gut microbiota dysbiosis and has good efficacy in treating antibiotic-associated diarrhea (AAD). In this study, we investigated the effects of sucrose, sorbitol, xylitol, and saccharin on the intestinal mucosal microbiota of AAD mice treated with QWBZP. When the AAD model was constructed by being gavaged mixed antibiotic solution, Kunming mice were randomly assigned to seven groups: the control (mn) group, the ADD (mm) group, the QWBZP (mq) group, the saccharin + QWBZP (mc) group, the sucrose + QWBZP (ms) group, the xylito + QWBZP (mx) group, and the sorbitol + QWBZP (msl) group. Subsequently, 16S rRNA gene amplicon sequencing was used to analyze the intestinal mucosal microbiota composition and abundance. The results showed that feces from AAD mice were diluted and wet and improved diarrhea symptoms with QWBZP and sorbitol. In contrast, the addition of sucrose, saccharin, and xylitol delayed the healing of diarrhea. The relative abundance of intestinal mucosal microbiota showed Glutamicibacter, Robinsoniella, and Blautia were characteristic bacteria of the mx group, Candidatus Arthromitus, and Bacteroidales_S24-7_group as the typical bacteria of the mn group, Clostridium_innocuum_group as the distinct bacteria of the mm group. Mycoplasma and Bifidobacterium as the characteristic bacteria of the ms group. Correlation analysis of typical bacterial genera with metabolic functions shows that Blautia negatively correlates with D-Glutamine and D-glutamate metabolism. Bacteroidales_S24-7_group has a significant negative correlation with the Synthesis and degradation of ketone bodies. The study confirmed that sucrose, sorbitol, xylitol, and saccharin might further influence metabolic function by altering the intestinal mucosal microbiota. Compared to the other sweetener, adding sorbitol to QWBZP was the best therapeutic effect for AAD and increased the biosynthesis and degradation activities. It provides the experimental basis for applying artificial sweeteners in traditional Chinese medicine (TCM) as a reference for further rational development and safe use of artificial sweeteners.

Project description:BACKGROUND:Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients. METHODS:A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed. RESULTS:Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU. CONCLUSION:In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU. TRIAL REGISTRATION:ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).

Project description:ImportanceThe efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear.ObjectiveTo assess the effect of a multispecies probiotic on the risk of AAD in children.Design, setting, and participantsThis randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial.InterventionsA multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after.Main outcomes and measuresThe primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications.ResultsA total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events.Conclusions and relevanceA multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation.Trial registrationClinicalTrials.gov Identifier: NCT03334604.

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Human intestinal microbiota gene risk factors for antibiotic-associated diarrhea: perspectives for prevention. Risk factors for antibiotic-associated diarrhea.

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Human intestinal microbiota gene risk factors for antibiotic-associated diarrhea: perspectives for prevention. Risk factors for antibiotic-associated diarrhea.

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