Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption.

Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis, the world's most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.

A Multimodal Desorption Electrospray Ionisation Workflow Enabling Visualisation of Lipids and Biologically Relevant Elements in a Single Tissue Section.

The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative and infectious diseases and are known to disrupt lipid metabolism. Desorption electrospray ionisation (DESI) is a widely used approach for molecular imaging, but previous work has shown that DESI delocalises ions such as potassium (K) and chlorine (Cl), precluding the subsequent elemental analysis of the same section of tissue. The solvent typically used for the DESI electrospray is a combination of methanol and water. Here we show that a novel solvent system, (50:50 (%v/v) MeOH:EtOH) does not delocalise elemental species and thus enables elemental mapping to be performed on the same tissue section post-DESI. Benchmarking the MeOH:EtOH electrospray solvent against the widely used MeOH:H2O electrospray solvent revealed that the MeOH:EtOH solvent yielded increased signal-to-noise ratios for selected lipids. The developed multimodal imaging workflow was applied to a lung tissue section containing a tuberculosis granuloma, showcasing its applicability to elementally rich samples displaying defined structural information.

Obesity and Loss of Kidney Function: Two Complications to Face for Older Living Kidney Donors.

OBJECTIVES: Although living kidney donors have a minimal lifetime risk of developing end-stage renal disease, long-term complications and physiologic and psychologic sequelae resulting from donation remain unclear because of lack of optimum follow-up after transplant. Here, we evaluated renal function, complications, and physical and mental performance of living kidney donors. MATERIALS AND METHODS: We evaluated 147 patients who donated living kidneys between 1981 and 2012 at Baskent University Hospital. We collected data on donor age, sex, body mass index, smoking status, hypertension before and after nephrectomy, proteinuria, estimated glomerular filtration rate according to the Modification of Diet in Renal Disease formula, and duration after donation. All donors answered the Medical Outcomes Study short-form general health survey; results were evaluated according to answers to 11 questions totaling 22 points. RESULTS: Body mass index of donors showed that 31 (21.1%) were in normal range, 66 (44.9%) had mild obesity (body mass index of 26-30 kg/m²), and 30 (34%) had moderate to high obesity (body mass index > 30 kg/m2). Results from the general health survey showed that 117 donors (80%) had no loss, 13 (9%) had mild loss, 12 (8%) had moderate loss, and 5 (3%) had high loss of ability. When we compared estimated glomerular filtration rates according to donor age, donors who were 18 to 34 years had a mean estimated glomerular filtration rate of 113.5 ± 40, donors 35 to 49 years had a mean rate of 95.01 ± 23.4, donors 50 to 64 years had a mean rate of 87.43 ± 25.4, and donors older than 65 years had a mean rate of 63.76 ± 11.35 mL/min/1.73 m², revealing a statistically significant loss of kidney function with aging (P = .001).. CONCLUSIONS: Careful evaluation of kidney donors before and after donation is essential for the most common risk factors, such as obesity, and for loss of kidney function, especially in older donors.