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植物乳杆菌MTCC 25433与槲皮素混合物改善小鼠模型中苯并[a]芘诱导的肠道失调

Lactiplantibacillus plantarum MTCC 25433 and Quercetin Blend Ameliorate Benzo[a]pyrene-Induced Gut Dysregulation in a Murine Model.

作者信息

Goyal Shivani Popli, Chandratre Gauri A, Rawat Anita, Kondepudi Kanthi Kiran, Badgujar Prarabdh C, Saravanan Chakkaravarthi

机构信息

Department of Inter-disciplinary Sciences, National Institute of Food Technology Entrepreneurship and Management, Sonipat, Haryana, 131028, India.

Department of Veterinary Public Health & Epidemiology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana, 125001, India.

出版信息

Curr Microbiol. 2025 Aug 4;82(9):434. doi: 10.1007/s00284-025-04411-x.

DOI:10.1007/s00284-025-04411-x
PMID:40760101
Abstract

Benzo[a]pyrene (B[a]P), a carcinogenic food contaminant, is implicated in colonic abnormalities, including colorectal cancer. This study evaluated the synergistic potential of a novel synbiotic blend of Lactiplantibacillus plantarum MTCC 25433 (9 log CFU/d) and quercetin (25 mg/kg/d) against B[a]P-induced gut dysregulation in Swiss albino mice. Oral B[a]P exposure (50 mg/kg, twice weekly for 28 days) disrupted the intestinal homeostasis, enhancing lipid peroxidation (+ 44.1%), proinflammatory cytokines levels (TNF-α: + 69.6%, IL-6: + 52.9%), inflammatory transcription factors (Nf-κB: 1.92-fold, Foxa2: 2.92-fold) and mucin expression (Muc-2: 2.9-fold), and perturbed gut barrier integrity (Occludin: 0.61-fold, Cldn-4: 0.14-fold). The synbiotic blend exhibited superior efficacy compared to MTCC 25433 or quercetin alone, mitigating MDA (- 32%), TNF-α (- 66%), IL-6 (- 59%), Nf-κB: - 38%, Foxa2: - 51%, Muc-2 (- 57%), Occludin (+ 129%) and Cld-4 (+ 352%) levels and further resulted in enhanced B[a]P fecal excretion (29.5 to 182 μg/g). Two-way ANOVA analysis confirmed synergistic interactions specifically for reductions in adipose tissue B[a]P levels, metabolic enzyme expression (Cyp1b1), gut barrier integrity (Cldn-4), and microbiome modulation, notably Firmicutes, Lachnospiraceae, Clostridium and Ruminococcus, along with enhanced butyrate concentrations. Histopathological analysis confirmed the protective effects of a synbiotic blend against B[a]P-mediated adipocyte disruption and necrosis in the hepatic and intestinal tissues. Principal component analysis also supported its synergistic efficacy in alleviating B[a]P toxicity. Overall, these findings demonstrated the potent anti-inflammatory, antioxidant and gut-modulating potential of the synbiotic blend, suggesting its potential as a promising dietary approach for mitigating the harmful effects of the food contaminant, B[a]P.

摘要

苯并[a]芘(B[a]P)是一种致癌性食品污染物,与包括结直肠癌在内的结肠异常有关。本研究评估了植物乳杆菌MTCC 25433(9 log CFU/d)和槲皮素(25 mg/kg/d)的新型合生元混合物对B[a]P诱导的瑞士白化小鼠肠道失调的协同作用潜力。口服B[a]P(50 mg/kg,每周两次,共28天)破坏了肠道稳态,增强了脂质过氧化(+44.1%)、促炎细胞因子水平(TNF-α:+69.6%,IL-6:+52.9%)、炎症转录因子(Nf-κB:1.92倍,Foxa2:2.92倍)和粘蛋白表达(Muc-2:2.9倍),并扰乱了肠道屏障完整性(闭合蛋白:0.61倍,紧密连接蛋白4:0.14倍)。与单独使用MTCC 25433或槲皮素相比,合生元混合物表现出更高的功效,减轻了丙二醛(-32%)、TNF-α(-66%)、IL-6(-59%)、Nf-κB(-38%)、Foxa2(-51%)、Muc-2(-57%)、闭合蛋白(+129%)和紧密连接蛋白4(+352%)的水平,并进一步导致B[a]P粪便排泄增加(29.5至182μg/g)。双向方差分析证实了在降低脂肪组织B[a]P水平、代谢酶表达(Cyp1b1)、肠道屏障完整性(紧密连接蛋白4)和微生物群调节(特别是厚壁菌门、毛螺菌科、梭菌属和瘤胃球菌属)方面存在协同相互作用,同时丁酸盐浓度增加。组织病理学分析证实了合生元混合物对B[a]P介导的肝脏和肠道组织中脂肪细胞破坏和坏死的保护作用。主成分分析也支持其在减轻B[a]P毒性方面的协同功效。总体而言,这些发现证明了合生元混合物具有强大的抗炎、抗氧化和肠道调节潜力,表明其作为一种有前景的饮食方法,可减轻食品污染物B[a]P的有害影响。

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