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.

Figure 1

Representative TTGE gel image of faecal microbiota DNA before antibiotic treatment. M control marker DNA.

Figure 2. Analysis of Variance (ANOVA)

Fisher F-values (AAD) are plotted against the migration distance. The Fisher F limit (threshold value) was obtained using randomisation procedures (see Methods). Six electrophoresis distances were found to exceed this threshold, and were thus considered significant.

Figure 3. Mean TTGE electrophoresis at D₀

The grey bars emphasize the regions detected by ANOVA tests. Solid line, pattern from patients with AAD; Dotted line, pattern from patients without ADD.

Figure 4. Comparison of ANOVA and discriminant analysis

Top: regions detected by ANOVA (grey bars) Bottom: first six variables introduced in forward discriminant analysis (vertical lines). Vertical lines are numbered in order of introduction of the corresponding variable. Solid line, pattern from patients with AAD; Dotted line, pattern from patients without AAD.