An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice.

Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component in response to HFD is the gut microbiome, which is significantly altered during obesity and represents a target for developing new therapeutic interventions to fight metabolic diseases. Here, we show that CO delivered to the gut by oral administration with a CO-releasing molecule (CORM-401) accumulates in faeces and enriches a variety of microbial species that were perturbed by a HFD regimen. Notably, Akkermansia muciniphila, which exerts salutary metabolic effects in mice and humans, was strongly depleted by HFD but was the most abundant gut species detected after CORM-401 treatment. Analysis of bacterial transcripts revealed a restoration of microbial functional activity, with partial or full recovery of the Krebs cycle, ß-oxidation, respiratory chain and glycolysis. Mice treated with CORM-401 exhibited normalization of several plasma and fecal metabolites that were disrupted by HFD and are dependent on Akkermansia muciniphila's metabolic activity, including indoles and tryptophan derivatives. Finally, CORM-401 treatment led to an improvement in gut morphology as well as reduction of inflammatory markers in colon and cecum and restoration of metabolic profiles in these tissues. Our findings provide therapeutic insights on the efficacy of CO as a potential prebiotic to combat obesity, identifying the gut microbiota as a crucial target for CO-mediated pharmacological activities against metabolic disorders.

Disseminated Tuberculosis Revealed by Conus Medullaris Tuberculoma.

A 29-year-old man from Comoros presented with rapidly progressive paraplegia and sexual dysfunction. Magnetic resonance imaging (MRI) showed a contrast-enhanced conus medullaris lesion. Differential diagnoses included tumors, abscesses, and inflammatory diseases. Neurosurgery was delayed to complete examinations. Cerebral MRI showed three abscesses. Body computed tomography scan showed supracentimetric polyadenopathies, pulmonary nodules, prostatic lesion, and enhanced seminal vesicle, with hypermetabolism on positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose scan. Histology of lymph node biopsy showed granulomatous infiltration without acid-fast bacilli, and positive polymerase chain reaction for Mycobacterium tuberculosis. Lymph node culture was positive after 2 months, urine culture after 3 weeks, but cerebrospinal fluid and sputum cultures were negative. A 1-year antituberculosis therapy was initiated, associated with corticosteroids because the patient developed tuberculosis-immune reconstitution syndrome, revealed by the recurrence of neurological symptoms. After 2 months the patient completely recovered and could run. MRI showed stability of the voluminous tuberculoma with decrease of medullary edema. Avoiding surgery in those cases may prevent iatrogenic neurological deterioration.