Tracing NAD+ metabolism uncovers adaptive coordination between host and microbiome during colitis.
| Title: | Tracing NAD+ metabolism uncovers adaptive coordination between host and microbiome during colitis. |
|---|---|
| Authors: | Alsaadi AI; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Welz L; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Pothakamury AA; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Gilloteau C; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Prasad P; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Yahia MS; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Sadler J; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Smith JD; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Jenkins BC; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Diven GS; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Bornhäuser J; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Mekdoud T; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Tian S; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Rosenstiel P; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Schreiber S; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Bisanz JE; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.; Aden K; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine l., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; McReynolds MR; Department of Biochemistry and Molecular Biology, The Huck Institute of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. |
| Source: | Research square [Res Sq] 2025 Dec 04. Date of Electronic Publication: 2025 Dec 04. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet ISSN: 2693-5015 (Electronic) Linking ISSN: 26935015 NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| Abstract: | Host-microbiota metabolic interactions critically regulate nicotinamide adenine dinucleotide (NAD+) homeostasis, and their disruption is increasingly linked to chronic diseases including inflammatory bowel disease (IBD). However, it remains unclear whether NAD+ dysregulation in IBD arises from impaired production, enhanced consumption, or both. Using multi-omics approaches and stable isotope-labeled NAD+ precursors administered via intravenous infusion in a murine model of dextran sulfate sodium (DSS)-induced colitis, we mapped tissue- and lumen-specific NAD+ metabolism under inflammatory stress. Our results reveal tissue-specific rewiring of NAD+ metabolism, with increased flux through the salvage pathway compensating for reduced de novo NAD+ synthesis from tryptophan. In parallel, microbial de novo NAD+ production was elevated, highlighting a cooperative host-microbiota response to inflammatory stress. These findings demonstrate differential regulation of NAD+ biosynthesis during acute colitis and underscore the dynamic interplay between host and microbial metabolism in maintaining NAD+ homeostasis under inflammatory conditions. |
| Competing Interests: | Additional Declarations: There is NO Competing Interest. |
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| Grant Information: | R35 GM151045 United States GM NIGMS NIH HHS; T32 GM108563 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: DSS colitis; IBD; NAD+; gut microbiota; nicotinamide; tryptophan |
| Entry Date(s): | Date Created: 20251211 Date Completed: 20251225 Latest Revision: 20251226 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12687811 |
| DOI: | 10.21203/rs.3.rs-8195970/v1 |
| PMID: | 41377969 |
| Database: | MEDLINE |
Journal Article; Preprint