title: Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity.
abstract: The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to carbohydrate metabolism, and to contribute to unravel the underlying mechanisms and consequences for health conditions. We measured the activity level of GIT carbohydrate-active enzymes toward 23 distinct sugars in adults patients (n = 2) receiving 14-d β-lactam therapy and in obese (n = 7) and lean (n = 5) adolescents. We observed that both 14 d antibiotic-treated and obese subjects showed higher and less balanced sugar anabolic capacities, with 40% carbohydrates being preferentially processed as compared with non-treated and lean patients. Metaproteome-wide metabolic reconstructions confirmed that the impaired utilization of sugars propagated throughout the pentose phosphate metabolism, which had adverse consequences for the metabolic status of the GIT microbiota. The results point to an age-independent positive association between GIT glycosidase activity and the body mass index, fasting blood glucose and insulin resistance (r ( 2) ≥ 0.95). Moreover, antibiotics altered the active fraction of enzymes controlling the thickness, composition and consistency of the mucin glycans. Our data and analyses provide biochemical insights into the effects of antibiotic usage on the dynamics of the GIT microbiota and pin-point presumptive links to obesity. The knowledge and the hypotheses generated herein lay a foundation for subsequent, systematic research that will be paramount for the design of "smart" dietary and therapeutic interventions to modulate host-microbe metabolic co-regulation in intestinal homeostasis.
authors.affiliation: Spanish National Research Council (CSIC), Institute of Catalysis, Madrid, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Hernández
authors.forename: Rafael
authors.initials: R
authors.lastname: Bargiela
authors.forename: María Suárez
authors.initials: MS
authors.lastname: Diez
authors.forename: Anette
authors.initials: A
authors.lastname: Friedrichs
authors.forename: Ana Elena
authors.initials: AE
authors.lastname: Pérez-Cobas
authors.forename: María José
authors.initials: MJ
authors.lastname: Gosalbes
authors.forename: Henrik
authors.initials: H
authors.lastname: Knecht
authors.forename: Mónica
authors.initials: M
authors.lastname: Martínez-Martínez
authors.forename: Jana
authors.initials: J
authors.lastname: Seifert
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Alejandro
authors.initials: A
authors.lastname: Artacho
authors.forename: Alicia
authors.initials: A
authors.lastname: Ruiz
authors.forename: Cristina
authors.initials: C
authors.lastname: Campoy
authors.forename: Amparo
authors.initials: A
authors.lastname: Latorre
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Ott
authors.forename: Andrés
authors.initials: A
authors.lastname: Moya
authors.forename: Antonio
authors.initials: A
authors.lastname: Suárez
authors.forename: Vitor A P
authors.initials: VA
authors.lastname: Martins dos Santos
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferrer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D058448:Biota; D015992:Body Mass Index; D050260:Carbohydrate Metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D006943:Hyperglycemia; D007333:Insulin Resistance; D008297:Male; D064307:Microbiota; D009765:Obesity
chemical_list: D000900:Anti-Bacterial Agents
keywords: antibiotic therapy; distal gut; glycosidase; metabolic reconstruction; obesity