{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:18:16Z","timestamp":1771928296366,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Ongoing refinements of multidrug regimens, and particularly the addition of L-asparaginase, resulted in an immediate gain in survival for pediatric acute lymphoblastic leukemia patients. Yet L-asparaginase has substantial side effects which may require dose reductions or delays in subsequent doses. There are at least 3 possible sources of L-asparagine to consider when balancing blood levels with asparaginase dosing, diet, cell synthesis and bacterial synthesis. To date, there is one precedent, in mice, in which blood L-asparagine levels are reduced as a consequence of reducing consumed levels. We build on that approach in experiments aimed at testing whether long-term dietary restriction of L-asparagine and possibly gut bacteria can impact blood levels. In our experiment, 2 groups of mice received food pellets with either 4% or 0% L-asparagine. Blood and fecal metabolites and fecal bacteria were sampled over 72 days. After this accommodation period, all mice continued their diet and received a single injection of pegylated\n                    <jats:italic>E. coli<\/jats:italic>\n                    recombinant L-asparaginase. Samples for bacteria and metabolites were collected 4 and 5 days later, respectively. Neither diet had adverse effects on the general health of the mice nor did diet alone change blood L-asparagine levels. Both diets led to changes in gut bacteria. L-asparaginase depleted blood L-asparagine in mice consuming either diet. Bacteria identified in fecal pellets revealed that the microbiomes of mice in the 2 cages were different (cage effect) and remained different although metagenomic analyses of day 72 feces indicated there were no diet-dependent differences in bacterial asparaginase or asparagine synthetase. These outcomes indicate that mice recover from any short-term down regulation of blood L-asparagine due to diet and consequently the metabolic controls become complex, and the gut microbes seem to not be a great influence. Further research should include approaches to determine the source of L-asparagine in the blood while ingesting diets with no\/low or high amounts of L-asparagine.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2025.1634113","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:26:13Z","timestamp":1769750773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating diet to control asparagine uptake as an adjunct to asparaginase treatment"],"prefix":"10.3389","volume":"15","author":[{"given":"Zara","family":"Forbrigger","sequence":"first","affiliation":[{"name":"Department of Pathology, Dalhousie University","place":["Halifax, NS, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, IWK Health","place":["Halifax, NS, 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