{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:30:16Z","timestamp":1764937816948,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003443","name":"The Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["FGMF-2022-0003","124021200031-4"],"award-info":[{"award-number":["FGMF-2022-0003","124021200031-4"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact of BNC on immune function, the intestinal microbiome, intestinal barrier integrity, and allergic sensitization in subacute experiments on rats. Male Wistar rats received BNC with a diet for eight weeks in a dose range of 1\u2013100 mg\/kg of body weight. The measurements of serum levels of cytokines, adipokines, iFABP2, indicators of cellular immunity, composition of the intestinal microbiome, and a histological study of the ileal mucosa were performed. In a separate four-week experiment on a model of systemic anaphylaxis to food antigen, BNC at a dose of 100 mg\/kg of body weight did not increase the severity of the reaction or change the response of IgG antibodies. Based on dose\u2013response effects on immune function, the non-observed adverse effect level for BNC was less than 100 mg\/kg of body weight per day. The effects of BNC on the gut microbiome and the intestinal mucosal barrier were not dose-dependent. Data on the possible presence of prebiotic effects in BNC have been obtained.<\/jats:p>","DOI":"10.3390\/nano14201678","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T03:57:09Z","timestamp":1729483029000},"page":"1678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Toxicological Characteristics of Bacterial Nanocellulose in an In Vivo Experiment\u2014Part 2: Immunological Endpoints, Influence on the Intestinal Barrier and Microbiome"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0015-8735","authenticated-orcid":false,"given":"Vladimir A.","family":"Shipelin","sequence":"first","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8897-347X","authenticated-orcid":false,"given":"Ekaterina A.","family":"Skiba","sequence":"additional","affiliation":[{"name":"Institute for Problems of Chemical and Energetic Technologies of the Siberian Branch of the Russian Academy of Sciences, 659322 Biysk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1628-0815","authenticated-orcid":false,"given":"Vera V.","family":"Budaeva","sequence":"additional","affiliation":[{"name":"Institute for Problems of Chemical and Energetic Technologies of the Siberian Branch of the Russian Academy of Sciences, 659322 Biysk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-4436","authenticated-orcid":false,"given":"Antonina A.","family":"Shumakova","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora N.","family":"Trushina","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana K.","family":"Mustafina","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-6412","authenticated-orcid":false,"given":"Yuliya M.","family":"Markova","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay A.","family":"Riger","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-6508","authenticated-orcid":false,"given":"Ivan V.","family":"Gmoshinski","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana A.","family":"Sheveleva","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey A.","family":"Khotimchenko","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"},{"name":"Department of Food Hygiene and Toxicology, Institute of Vocational Education, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry B.","family":"Nikityuk","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 109240 Moscow, Russia"},{"name":"Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"},{"name":"Department of Ecology and Food Safety, Institute of Ecology, Peoples\u2019 Friendship University of Russia Named After Patrice Lumumba, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Azeredo, H.M.C., Barud, H., Farinas, C.S., Vasconcellos, V.M., and Claro, A.M. (2019). Bacterial cellulose as a raw material for food and food packaging applications. Front. Sustain. Food Syst., 3.","DOI":"10.3389\/fsufs.2019.00007"},{"key":"ref_2","first-page":"1","article-title":"Bacterial nanocellulose: What future?","volume":"8","author":"Dourado","year":"2018","journal-title":"Bioimpacts"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gama, M., Dourado, F., and Bielecki, S. (2016). Celluloses as food ingredients\/additives: Is there room for BNC?. Bacterial Nanocellulose 1st Edition: From Biotechnology to Bio-Economy, Elsevier. eISBN: 9780444634665.","DOI":"10.1016\/B978-0-444-63458-0.00007-X"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijfoodmicro.2015.12.015","article-title":"Kombucha tea fermentation: Microbial and biochemical dynamics","volume":"220","author":"Chakravorty","year":"2016","journal-title":"Int. J. Food Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cubas, A.L.V., Provin, A.P., Dutra, A.R.A., Mouro, C., and Gouveia, I.C. (2023). Advances in the production of biomaterials through kombucha using food waste: Concepts, challenges, and potential. Polymers, 15.","DOI":"10.3390\/polym15071701"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhong, C. (2020). Industrial-Scale Production and Applications of Bacterial Cellulose. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.605374"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Quijano, L., Rodrigues, R., Fischer, D., Tovar-Castro, J.D., Payne, A., Navone, L., Hu, Y., Yan, H., Pinmanee, P., and Poon, E. (2024). Bacterial Cellulose Cookbook: A Systematic Review on Sustainable and Cost-Effective Substrates. J. Bioresour. Bioprod., in press.","DOI":"10.1016\/j.jobab.2024.05.003"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/17435390.2022.2069057","article-title":"Overview of potential adverse health effects of oral exposure to nanocellulose","volume":"16","author":"Brand","year":"2022","journal-title":"Nanotoxicology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110346","DOI":"10.1016\/j.jfoodeng.2020.110346","article-title":"The behavior of nanocellulose in gastrointestinal tract and its influence on food digestion","volume":"292","author":"Liu","year":"2021","journal-title":"J. Food Eng."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shavyrkina, N.A., Budaeva, V.V., Skiba, E.A., Mironova, G.F., Bychin, N.V., Gismatulina, Y.A., Kashcheyeva, E.I., Sitnikova, A.E., Shilov, A.I., and Kuznetsov, P.S. (2021). Scale-up of biosynthesis process of bacterial nanocellulose. Polymers, 13.","DOI":"10.3390\/polym13121920"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shipelin, V.A., Skiba, E.A., Budayeva, V.V., Shumakova, A.A., Kolobanov, A.I., Sokolov, I.E., Maisaya, K.Z., Guseva, G.V., Trusov, N.V., and Masyutin, A.G. (2024). Toxicological Characteristics of Bacterial Nanocellulose in an In Vivo Experiment\u2014Part 1: The Systemic Effects. Nanomaterials, 14.","DOI":"10.3390\/nano14090768"},{"key":"ref_12","unstructured":"(2015). Nanotechnologies\u2014Vocabulary Part 2: Nano-Objects (Standard No. ISO\/TS 80004-2)."},{"key":"ref_13","unstructured":"Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research (ILAR), Division on Earth and Life Studies (DELS), and National Research Council of the National Academies (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [8th ed.]."},{"key":"ref_14","unstructured":"Holt, J.G., and Krieg, H.R. (1984). Bergey\u2019s Manual of Systematic Bacteriology, Williams and Wilkins. [9th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12986-016-0089-7","article-title":"The role of I-FABP as a biomarker of intestinal barrier dysfunction driven by gut microbiota changes in obesity","volume":"13","author":"Lau","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3109\/10915819109078651","article-title":"Toxicologic evaluation of cellulon fiber; genotoxicity, pyrogenicity, acute and subchronic toxicity","volume":"10","author":"Schmitt","year":"1991","journal-title":"J. Am. Coll. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.carbpol.2015.10.071","article-title":"Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses","volume":"137","author":"Pinto","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2131\/jts.35.317","article-title":"\u0410 28-day oral toxicity study of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, in F344 rats","volume":"35","author":"Hagiwara","year":"2010","journal-title":"J. Toxicol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.imlet.2020.04.004","article-title":"Immunological aspects of nanocellulose","volume":"222","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/1040841X.2018.1426556","article-title":"Bacterial pathogenesis and interleukin-17: Interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection","volume":"44","author":"Chamoun","year":"2018","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.4049\/jimmunol.1600138","article-title":"IL-17 promotes neutrophil-mediated immunity by activating microvascular pericytes and not endothelium","volume":"197","author":"Liu","year":"2016","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kartasheva-Ebertz, D., Gaston, J., Lair-Mehiri, L., Mottez, E., Buivan, T.P., Massault, P.P., Scatton, O., Gaujoux, S., Vaillant, J.C., and Pol, S. (2022). IL-17A in human liver: Significant source of inflammation and trigger of liver fibrosis initiation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179773"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.biomaterials.2019.02.025","article-title":"Cellulose nanocrystals modulate alveolar macrophage phenotype and phagocytic function","volume":"203","author":"Ervik","year":"2019","journal-title":"Biomaterials"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/toxres\/tfaa082","article-title":"Physical, chemical, and toxicological characterization of sulfated cellulose nanocrystals for food-related applications using in vivo and in vitro strategies","volume":"9","author":"Ede","year":"2020","journal-title":"Toxicol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.toxrep.2020.01.003","article-title":"A 90-day dietary study with fibrillated cellulose in Sprague-Dawley rats","volume":"7","author":"Ong","year":"2020","journal-title":"Toxicol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100216","DOI":"10.1016\/j.impact.2020.100216","article-title":"Effects of ingested nanocellulose on intestinal microbiota and homeostasis in Wistar Han rats","volume":"18","author":"Khare","year":"2020","journal-title":"NanoImpact"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Casado, M.E., Collado-P\u00e9rez, R., Frago, L.M., and Barrios, V. (2023). Recent advances in the knowledge of the mechanisms of leptin physiology and actions in neurological and metabolic pathologies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021422"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"600","DOI":"10.25122\/jml-2021-0153","article-title":"Leptin hormone and its effectiveness in reproduction, metabolism, immunity, diabetes, hopes and ambitions","volume":"14","author":"Alburghaif","year":"2021","journal-title":"J. Med. Life"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1189\/jlb.68.4.437","article-title":"Leptin in the regulation of immunity, inflammation, and hematopoiesis","volume":"68","author":"Fantuzzi","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lopes, V.R., Str\u00f8mme, M., and Ferraz, N. (2020). In vitro biological impact of nanocellulose fibers on human gut bacteria and gastrointestinal cells. Nanomaterials, 10.","DOI":"10.3390\/nano10061159"},{"key":"ref_31","first-page":"100118","article-title":"A systematic review on the effects of nanomaterials on gut microbiota","volume":"3","author":"Utembe","year":"2022","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"A290","DOI":"10.1289\/ehp.115-a290a","article-title":"Concepts of nanoparticle dose metric and response metric","volume":"115","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cbi.2018.02.015","article-title":"Renal toxicological evaluations of sulphonated nanocellulose from Khaya sengalensis seed in Wistar rats","volume":"284","author":"Adewuyi","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mota, R., Rodrigues, A.C., Silva-Carvalho, R., Costa, L., Martins, D., Sampaio, P., Dourado, F., and Gama, M. (2022). Tracking Bacterial Nanocellulose in Animal Tissues by Fluorescence Microscopy. Nanomaterials, 12.","DOI":"10.3390\/nano12152605"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1039\/C9EN00184K","article-title":"Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models","volume":"6","author":"DeLoid","year":"2019","journal-title":"Environ. Sci. Nano"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/jn\/117.2.253","article-title":"Intestinal structural changes in african green monkeys after long term psyllium or cellulose feeding","volume":"117","author":"Paulini","year":"1987","journal-title":"J. Nutr."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/20\/1678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:16:39Z","timestamp":1760112999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/20\/1678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,19]]},"references-count":36,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["nano14201678"],"URL":"https:\/\/doi.org\/10.3390\/nano14201678","relation":{},"ISSN":["2079-4991"],"issn-type":[{"type":"electronic","value":"2079-4991"}],"subject":[],"published":{"date-parts":[[2024,10,19]]}}}