A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes

<i>Ralstonia eutropha</i> H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety...

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Main Authors: Xiaoyan You, Shuxia Song, Bing Li, Hui Wang, Le Zhang, Xiangyang Li, Junliang Chen, Zhiguang Zhu, Guoping Zhao
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/6/1323
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author Xiaoyan You
Shuxia Song
Bing Li
Hui Wang
Le Zhang
Xiangyang Li
Junliang Chen
Zhiguang Zhu
Guoping Zhao
author_facet Xiaoyan You
Shuxia Song
Bing Li
Hui Wang
Le Zhang
Xiangyang Li
Junliang Chen
Zhiguang Zhu
Guoping Zhao
author_sort Xiaoyan You
collection DOAJ
description <i>Ralstonia eutropha</i> H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety evaluations remain insufficient for food-grade applications. This study systematically assessed the safety of <i>R. eutropha</i> H16 through genomic, phenotypic, and toxicological analyzes. Genomic analyzes revealed the absence or minimal presence of virulence factors and antibiotic resistance genes, aligning with microbiological safety standards. Phenotypic investigations demonstrated a limited gastric fluid tolerance (pH 2.5, survival rate 25.70% after 3 h) and intestinal fluid persistence (pH 8, 44.67% viability after 3 h), coupled with an exceptional bile salt tolerance (0.2% <i>w</i>/<i>v</i>). Antioxidant assays confirmed the fermentation broth specifically scavenges DPPH free radicals (14.60 ± 1.24 μg Trolox/mL), whereas bacterial suspensions and cell-free supernatants exhibited a strong hydroxyl radical scavenging (>90 U/mL) and superoxide anion inhibition (>100 U/L). Acute toxicity testing indicated no mortality or histopathological abnormalities, with an LD<sub>50</sub> value exceeding 1 × 10¹¹ CFU/kg. Subacute toxicity studies (28-day, 1 × 10<sup>8</sup>–1 × 10<sup>10</sup> CFU/kg) revealed no significant effects on growth, hematology, or organ function. Minor alterations in serum biochemistry might be attributed to physiological adaptation. Subacute exposure induced transient serum ALT fluctuations without hepatorenal dysfunction, while maintaining hematological parameters within physiological ranges. Collectively, these results substantiate the safety of <i>R. eutropha</i> H16 for food-related applications while underscoring the necessity of strain-specific risk assessments for industrial microbial platforms.
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spelling doaj-art-4e8d2a05c2c84ffeb1650dd36cab828b2025-08-20T03:29:35ZengMDPI AGMicroorganisms2076-26072025-06-01136132310.3390/microorganisms13061323A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological AnalyzesXiaoyan You0Shuxia Song1Bing Li2Hui Wang3Le Zhang4Xiangyang Li5Junliang Chen6Zhiguang Zhu7Guoping Zhao8Henan Engineering Research Center of Food Microbiology, College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, ChinaHenan Engineering Research Center of Food Microbiology, College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, ChinaNational Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Tianjin 300308, ChinaNational Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Tianjin 300308, ChinaHenan Engineering Research Center of Food Microbiology, College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, ChinaHenan Engineering Research Center of Food Microbiology, College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, ChinaHenan Engineering Research Center of Food Microbiology, College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, ChinaNational Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Tianjin 300308, ChinaNational Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Tianjin 300308, China<i>Ralstonia eutropha</i> H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety evaluations remain insufficient for food-grade applications. This study systematically assessed the safety of <i>R. eutropha</i> H16 through genomic, phenotypic, and toxicological analyzes. Genomic analyzes revealed the absence or minimal presence of virulence factors and antibiotic resistance genes, aligning with microbiological safety standards. Phenotypic investigations demonstrated a limited gastric fluid tolerance (pH 2.5, survival rate 25.70% after 3 h) and intestinal fluid persistence (pH 8, 44.67% viability after 3 h), coupled with an exceptional bile salt tolerance (0.2% <i>w</i>/<i>v</i>). Antioxidant assays confirmed the fermentation broth specifically scavenges DPPH free radicals (14.60 ± 1.24 μg Trolox/mL), whereas bacterial suspensions and cell-free supernatants exhibited a strong hydroxyl radical scavenging (>90 U/mL) and superoxide anion inhibition (>100 U/L). Acute toxicity testing indicated no mortality or histopathological abnormalities, with an LD<sub>50</sub> value exceeding 1 × 10¹¹ CFU/kg. Subacute toxicity studies (28-day, 1 × 10<sup>8</sup>–1 × 10<sup>10</sup> CFU/kg) revealed no significant effects on growth, hematology, or organ function. Minor alterations in serum biochemistry might be attributed to physiological adaptation. Subacute exposure induced transient serum ALT fluctuations without hepatorenal dysfunction, while maintaining hematological parameters within physiological ranges. Collectively, these results substantiate the safety of <i>R. eutropha</i> H16 for food-related applications while underscoring the necessity of strain-specific risk assessments for industrial microbial platforms.https://www.mdpi.com/2076-2607/13/6/1323<i>Ralstonia eutropha</i> H16safety assessmentphenotypic analysisacute and subacute toxicity
spellingShingle Xiaoyan You
Shuxia Song
Bing Li
Hui Wang
Le Zhang
Xiangyang Li
Junliang Chen
Zhiguang Zhu
Guoping Zhao
A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
Microorganisms
<i>Ralstonia eutropha</i> H16
safety assessment
phenotypic analysis
acute and subacute toxicity
title A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
title_full A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
title_fullStr A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
title_full_unstemmed A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
title_short A Comprehensive Safety Assessment of <i>Ralstonia eutropha</i> H16 for Food Applications: Integrating Genomic, Phenotypic, and Toxicological Analyzes
title_sort comprehensive safety assessment of i ralstonia eutropha i h16 for food applications integrating genomic phenotypic and toxicological analyzes
topic <i>Ralstonia eutropha</i> H16
safety assessment
phenotypic analysis
acute and subacute toxicity
url https://www.mdpi.com/2076-2607/13/6/1323
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