Engineered Lactobacillus rhamnosus Producing 3-Hydroxybutyrate: A Dual-Action Therapeutic Strategy for Colon Cancer Cachexia

IF 3.6 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Xu Qiu, Zhiyun Zou, Taijie Lin, Chenyun Guo, Donghai Lin
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Abstract

3-hydroxybutyrate (3-HB), an essential endogenous metabolite, shows significant therapeutic potential in several disease contexts. However, its clinical application has been hampered by limitations, such as adverse effects on the gut microbiota. This study introduces a genetically engineered strain of Lactobacillus rhamnosus GG (LGGK) that integrates the benefits of 3-HB production with the probiotic properties of LGG. Using a murine colon cancer cachexia (CAC) model, LGGK supplementation significantly improved survival, reduced tumor progression, and alleviated muscle wasting. LGGK restored gut microbial diversity, increased the abundance of beneficial bacteria, and increased the production of short-chain fatty acids while reducing harmful microbial populations. In addition, LGGK supplementation demonstrated anti-inflammatory effects, effectively reducing elevated pro-inflammatory cytokines in serum and skeletal muscle. These findings highlight LGGK as a dual-action therapeutic approach that utilizes the metabolic benefits of 3-HB and the gut-modulating properties of LGG. This innovation offers a promising strategy for the treatment of CAC and potentially other metabolic and inflammatory disorders, and highlights the potential of engineered probiotics in advanced therapeutic applications.

Abstract Image

Abstract Image

产生3-羟基丁酸的工程鼠李糖乳杆菌:结肠癌恶病质的双作用治疗策略
3-羟基丁酸盐(3-HB)是一种重要的内源性代谢物,在几种疾病中显示出显著的治疗潜力。然而,它的临床应用一直受到限制,如对肠道微生物群的不良影响。本研究介绍了一种鼠李糖乳杆菌GG (LGGK)基因工程菌株,该菌株将3-HB生产的益处与LGG的益生菌特性结合在一起。在小鼠结肠癌恶病质(CAC)模型中,补充LGGK可显著提高生存率,减少肿瘤进展,减轻肌肉萎缩。LGGK恢复了肠道微生物的多样性,增加了有益菌的丰度,增加了短链脂肪酸的产生,同时减少了有害微生物的数量。此外,补充LGGK显示出抗炎作用,有效降低血清和骨骼肌中升高的促炎细胞因子。这些发现强调了LGGK作为一种双重作用的治疗方法,利用了3-HB的代谢益处和LGG的肠道调节特性。这一创新为治疗CAC和潜在的其他代谢和炎症性疾病提供了一种有前途的策略,并突出了工程益生菌在高级治疗应用中的潜力。
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来源期刊
Biotechnology and Bioengineering
Biotechnology and Bioengineering 工程技术-生物工程与应用微生物
CiteScore
7.90
自引率
5.30%
发文量
280
审稿时长
2.1 months
期刊介绍: Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.
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