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Bacteroides-associated NAD⁺ depletion correlates with exacerbated radiation-induced colorectal injury and impaired mucosal proliferative capacity - PubMed

2 days ago
  • #NAD metabolism
  • #Bacteroides
  • #Radiation proctitis
  • Radiation proctitis (RP) is a common complication of pelvic radiotherapy affecting treatment and quality of life.
  • Severe RP cases showed enrichment of Bacteroidales, while mild cases had more Firmicutes in fecal microbiomes.
  • Severe RP was linked to reduced NAD�� levels and increased microbial nicotinate/nicotinamide metabolism genes, particularly from Bacteroides species.
  • Fecal microbiota transplantation from severe-RP donors worsened radiation-induced colorectal injury in mice, lowering NAD�� levels.
  • Bacteroides gavage in mice worsened pathology, reduced mitochondrial membrane potential, and decreased Lgr5�� stem-cell proportion and proliferative indices.
  • Nicotinamide mononucleotide (NMN) supplementation attenuated injury and restored NAD�� levels, reversing Bacteroides-induced effects.
  • The study suggests Bacteroidales enrichment correlates with NAD�� depletion and exacerbated radiation-induced colorectal injury, offering potential microbiome- and metabolite-targeted therapies.