{"doi":"10.1016/j.celrep.2022.110738","title":"Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition","abstract":"Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a prominent, colonization-discriminatory, taxon-specific metabolite. Guided by bioinformatic analyses of biochemically validated TIRs, we find that acute malnutrition is associated with decreased fecal levels of genes encoding TIRs known or predicted to generate v-cADPR-x, as well as decreased levels of the metabolite itself. These results underscore the need to consider microbiome TIR NADases when evaluating NAD metabolism in the human holobiont.","journal":"Cell Reports","year":2022,"id":270098,"datarank":0.7017539347976732,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.29554640463234166,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.29554640463234166,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":9,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01889329"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":797451,"name":"Mark A. Zaydman","orcid":"0000-0002-4236-1459","position":1,"is_corresponding":false},{"id":933809,"name":"Siddarth Venkatesh","orcid":"0000-0002-4917-2693","position":2,"is_corresponding":false},{"id":267988,"name":"Yo Sasaki","orcid":"0000-0003-0024-0031","position":3,"is_corresponding":false},{"id":844220,"name":"Neha Damaraju","orcid":"0000-0002-5277-8653","position":4,"is_corresponding":false},{"id":933810,"name":"Alex L. Yenkin","orcid":"0000-0001-5909-7802","position":5,"is_corresponding":false},{"id":240471,"name":"William Buchser","orcid":"0000-0002-6675-6359","position":6,"is_corresponding":false},{"id":314949,"name":"Dmitry A. Rodionov","orcid":"0000-0002-0939-390X","position":7,"is_corresponding":false},{"id":42087,"name":"Andrei L. Osterman","orcid":"0000-0002-3810-9824","position":8,"is_corresponding":false},{"id":52795,"name":"Tahmeed Ahmed","orcid":"0000-0002-4607-7439","position":9,"is_corresponding":false},{"id":314951,"name":"Michael J. Barratt","orcid":"0000-0003-3794-1296","position":10,"is_corresponding":false},{"id":256133,"name":"Aaron DiAntonio","orcid":"0000-0002-7262-0968","position":11,"is_corresponding":false},{"id":240472,"name":"Jeffrey Milbrandt","orcid":"0000-0002-5477-7689","position":12,"is_corresponding":false},{"id":19791,"name":"Jeffrey I. Gordon","orcid":"0000-0001-8304-3548","position":13,"is_corresponding":false},{"id":844222,"name":"James Weagley","orcid":"0000-0001-5050-773X","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:27:26.772098Z","pmid":"35476981","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}