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 (r2 ≥ 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.

Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses

“…We reasoned that the decreased activity of putrescine-modifying enzymes may result in reduced production of N-acetylputrescine inside gut bacterial cells. This theory was further confirmed biochemically by activity tests in which the extension of the biochemical production of N-acetylputrescine from its reaction substrate putrescine (plus acetyl-CoA) was evaluated using microbial protein extracts obtained as described previously (Hernández et al, 2013). The results revealed that the carriage of toxigenic C. difficile is associated with microbial protein extracts (n = 6) that are not able to metabolise putrescine, whereas it was transformed to N-acetylputrescine and CoA in patients (n = 4) with toxin − C. difficile (25.0% ± 4.0% conversion to CoA) and in non-colonised controls (82.5 ± 8.4% conversion to CoA; n = 6) at the end of the assay.…”

“…Biochemical tests: transformation of putrescine to N-acetylputrescine Protein extracts from each of the patients were obtained as previously described (Hernández et al, 2013), using bacterial pellets separated from faecal material, as described above. Note that the bacterial cells were from the same batch used for metabolite extraction.…”

The art of targeting gut microbiota for tackling human obesity

“…An increased production of SCFA is thought to be characteristic from the obese microbiome (Fava et al 2013). In addition, it has been suggested that antibiotic uptake may interfere with sugar anabolic capacity of the microbiota by altering the enzymes controlling consistency, composition and thickness of mucin glycans (Hernandez et al 2013). An attenuated production of growth depressing toxins has also been proposed (Feighner and Dashkevicz 1987); (iii) Weakening of the innate immunity: as a consequence of antibiotic use, the low diversity induced in the microbiota can decrease the amount of receptors of microorganism-associated molecular patterns (MAMP) (Dessein et al 2009;Wells et al 2010).…”

Beyond gut microbiota: understanding obesity and type 2 diabetes

“…[90][91][92] However, there are some data that link antibiotic exposure to obesity risk. [93][94][95] Thus, while in mice models the available data suggest that gut microbiota is a realistic target, in humans it remains uncertain whether antibiotics use might be associated with metabolic improvement.…”