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Lack of genotoxicity and subchronic toxicity in safety assessment studies of formulation.

作者信息

Yu Esther, Eid John, Cheng Andrew, Lynch Barry, Bauter Mark

机构信息

Pendulum Therapeutics, Inc., 933 20th Street, San Francisco, CA 94107, United States.

Intertek Health Sciences Inc., 2233 Argentia Road, Suite 201, Mississauga, ON L5N 2×7, Canada.

出版信息

Toxicol Rep. 2024 Oct 26;13:101790. doi: 10.1016/j.toxrep.2024.101790. eCollection 2024 Dec.


DOI:10.1016/j.toxrep.2024.101790
PMID:39554606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11565037/
Abstract

A powder formulation of viable bacteria (AMUC) was evaluated in a 90-day repeated-dose toxicity study in rats and a battery of genotoxicity studies to evaluate AMUC as a food ingredient. All studies followed Organisation for Economic Co-operation and Development protocols (OECD TG 408, 471 473, 474). AMUC was administered to rats gavage at 0, 500, 1000, and 2000 mg/kg body weight/day (equivalent to 0, 4.1 × 10, 9.2 × 10, and 1.64 × 10 CFU/kg body weight/day). No mortality or treatment-related adverse effects were reported in any endpoints that were attributed to AMUC consumption. No bacterial translocation of viable from the intestinal tract was found to the liver, mesenteric lymph nodes, or blood. The no-observed-adverse-effect level was concluded to be the highest dose tested (2000 mg/kg body weight/day), approximately 1.64 × 10 CFU/kg body weight/day. AMUC (nonviable) was not mutagenic when examined in an bacterial reverse mutation assay and not clastogenic in an mammalian chromosomal aberration test. Viable AMUC was not genotoxic when evaluated in an mammalian cell micronucleus assay when administered at up to 1.64 ×10 CFU/kg body weight/day. These results confirm that AMUC is not toxic under the conditions of these studies.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fec7/11565037/cb0c96454adb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fec7/11565037/cb0c96454adb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fec7/11565037/cb0c96454adb/gr1.jpg

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本文引用的文献

[1]
Characterization and Preliminary Safety Evaluation of PROBIO.

Foods. 2024-1-30

[2]
Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.

PLoS One. 2024

[3]
The relationship between thyroid and human-associated microbiota: A systematic review of reviews.

Rev Endocr Metab Disord. 2024-2

[4]
Live and pasteurized Akkermansia muciniphila decrease susceptibility to Salmonella Typhimurium infection in mice.

J Adv Res. 2023-10

[5]
Safety Evaluation and Probiotic Potency Screening of Akkermansia muciniphila Strains Isolated from Human Feces and Breast Milk.

Microbiol Spectr. 2023-2-14

[6]
and in Immune-Related Diseases.

Microorganisms. 2022-11-30

[7]
suppressing nonalcoholic steatohepatitis associated tumorigenesis through CXCR6 natural killer T cells.

Front Immunol. 2022

[8]
Characterization of antibiotic-resistance traits in Akkermansia muciniphila strains of human origin.

Sci Rep. 2022-11-12

[9]
Rational consideration of Akkermansia muciniphila targeting intestinal health: advantages and challenges.

NPJ Biofilms Microbiomes. 2022-10-17

[10]
Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases.

Clin Nutr. 2022-10

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