Resilience of the Dominant Human Fecal Microbiota upon Short-Course Antibiotic Challenge

Abstract

Recent studies have shown that the human fecal microbiota is composed of a consortium of species specific to the host and resistant to modifications over time. Antibiotics are known to affect the intestinal microflora, and ensuing changes may result in antibiotic-associated diarrhea. It is therefore important to characterize the nature and amplitude of these modifications and the ability of this ecosystem to return to its original profile-i.e., its resilience. Six healthy volunteers received oral amoxicillin (1.5 g/day) for 5 days. Fecal samples were collected at day 0 (D0) before antibiotic treatment and at set intervals until 60 days thereafter. Fecal DNA was isolated, and V6-to-V8 regions of the 16S rRNA genes were amplified by PCR with general primers and analyzed by temporal temperature gradient gel electrophoresis. Dominant species profiles were compared on the basis of similarity (Pearson correlation coefficient). Dominant species profiles at D0 were used as a reference. The fecal microbiota showed a major shift in dominant species upon antibiotic treatment, starting 24 h after treatment initiation and reaching an average similarity of only 74% after 4 days. Within 30 days following antibiotic treatment, the fecal microbiota tended to reach an average similarity of 88% to the D0 value; within 60 days, the average similarity to the D0 value was 89%. However, in one subject, important modifications persisted for at least 2 months, with similarity to the D0 value remaining below 70%. We demonstrated the resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. Yet the persistence of long-term alterations in some subjects may explain susceptibilities to antibioticassociated diarrhea. Furthermore, these findings suggest that strategies reinforcing the ability of the fecal microbiota to resist modifications would be of clinical relevance.The human intestinal tract harbors a large, active, and complex community of microbes (22). The intestinal microbiota plays several significant roles in the digestion of food, metabolism of endogenous and exogenous compounds, immunopotentiation, and prevention of colonization by pathogens in the gastrointestinal tract and hence is involved in maintaining human health (12). Recent culture-independent molecular studies on healthy individuals have shown that the intestinal microbiota is specific to the host and resistant to modifications over time (26).Molecular analysis of the bacterial microbiota based on the 16S rRNA genes have attracted attention as reliable methods for detection and identification of bacterial species (9,13,14).

Long-term ecological impacts of antibiotic administration on the human intestinal microbiota

“…It is known that antimicrobial agents not only affect the pathogens to which they are directed but may also impact other members of the intestinal microbiota (Sjö lund et al, 2003;De La Cochetiere et al, 2005). Thus they inhibit susceptible organisms and select for resistant ones.…”

“…Thus they inhibit susceptible organisms and select for resistant ones. A number of different molecular fingerprinting techniques have previously been used to analyse the impact of antibiotics on the faecal microbiota such as denaturing or temperature gradient gel electrophoresis (DGGE or TGGE) (Donskey et al, 2003;Harmoinen et al, 2004), temporal TGGE (TTGE) (De La Cochetiere et al, 2005), terminal restriction fragment length polymorphism (T-RFLP) (Jernberg et al, 2005;Engelbrektson et al, 2006) and denaturing high-performance liquid chromatography (DHPLC) (Goldenberg et al, 2006). These techniques all bypass the necessity for cultivation, enabling comparative analyses of community fingerprints and the ability to monitor relative shifts in specific populations.…”

Effect of Antibiotic Therapy on Human Fecal Microbiota and the Relation to the Development of Clostridium difficile

“…Although, the difficulty to identify the exact profile at equilibrium has already been discussed [6], to take into account every patient's data including factors such as age, sex, clinical and/or antibiotherapy, is rather difficult. It needs the help of an abstract model that uses mathematical language to describe the behavior of the system by a set of variables and a set of equations that establish relationships between the variables.…”

Parenteral long-acting amoxicillin reduces intestinal bacterial community diversity in piglets even 5 weeks after the administration

“…Nevertheless, only a limited number of studies has assessed the prolonged impact of antibiotic treatment on gut microbiota. Recently, de la Cochetière et al (2005) reported a decrease in temporal temperature gradient gel electrophoresis profile similarities after 5-day oral administration of amoxicillin (500 mg 3 Â daily), confirming changes in the human fecal bacterial community.…”

“…Although another band (g), indicative of a butyrate-producing bacterium, was only observed in two of the treated animals, our results overall indicated a strong negative effect of parenteral long-acting amoxicillin on butyrate-producing populations related to Roseburia species. Interestingly, de la Cochetière et al (2005) observed an appearance of bands matching other Clostridium cluster XIVa bacteria, Clostridium nexile and Ruminococcus torques 3 and 4 days after commencing antibiotic treatment, which were absent before amoxicillin was introduced and after the end of the treatment, on days 30 and 60. This apparent effect of amoxicillin treatment on individual populations of butyrate producing bacteria in colon has not been previously investigated and should be the subject of further studies aiming at its functional implications for the developing gut ecosystem.…”