RT Journal Article
SR Electronic
T1 Gut microbiota disturbance during antibiotic therapy: a multi-omic approach
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1591
OP 1601
DO 10.1136/gutjnl-2012-303184
VO 62
IS 11
A1 Ana Elena Pérez-Cobas
A1 María José Gosalbes
A1 Anette Friedrichs
A1 Henrik Knecht
A1 Alejandro Artacho
A1 Kathleen Eismann
A1 Wolfgang Otto
A1 David Rojo
A1 Rafael Bargiela
A1 Martin von Bergen
A1 Sven C Neulinger
A1 Carolin Däumer
A1 Femke-Anouska Heinsen
A1 Amparo Latorre
A1 Coral Barbas
A1 Jana Seifert
A1 Vitor Martins dos Santos
A1 Stephan J Ott
A1 Manuel Ferrer
A1 Andrés Moya
YR 2013
UL http://gut.bmj.com/content/62/11/1591.abstract
AB Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated. Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation. Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.