Fuke Nobuo, Desaka Natsumi, Nakazawa Yuichiro, Suzuki Shigenori, Matsumoto Kenji, Higashimura Yasuki
Diet & Well-being Research Institute, KAGOME CO., LTD., Nasushiobara, Tochigi, Japan.
Department of Food Science, Ishikawa Prefectural University, Nonoichi, Ishikawa, Japan.
PLoS One. 2025 Sep 5;20(9):e0331446. doi: 10.1371/journal.pone.0331446. eCollection 2025.
Epidemiological studies in humans have suggested that tomato consumption and the compositional ratios of Prevotella, Megamonas, and Streptococcus in the intestinal microbiota are related to intestinal permeability. In this study, we investigated the causal relationship using Caenorhabditis (C.) elegans. We cultured Escherichia coli OP50 (the standard C. elegans food), Prevotella (P.) copri JCM 13464T, Megamonas funiformis JCM 14723T, and Streptococcus salivarius JCM 5707T in either normal medium or medium containing 1% (v/v) tomato juice (TJ medium), fed these bacteria to C. elegans for three days, and evaluated intestinal permeability using the Smurf assay. The proportion of Smurf individuals was significantly lower in C. elegans fed P. copri cultured in TJ medium than in those fed the same bacteria cultured in normal medium, while other strains showed no such medium-dependent differences. Interestingly, heat-killed P. copri grown in normal medium also reduced the proportion of Smurf individuals. Furthermore, P. copri grown in TJ medium exhibited a lower survival rate after seeding on nematode growth medium, an effect not observed in other strains. Liquid chromatography-tandem mass spectrometry analysis revealed that P. copri cultured in TJ medium accumulated L-(-)-3-phenyllactic acid (L-(-)-3-PLA), a compound known for its antibacterial properties through oxidative stress and its protective effects on the intestinal barrier. In contrast, the levels of known antioxidants such as 2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid and Cyclo(phenylalanyl-prolyl) were decreased. Culturing P. copri in normal medium supplemented with L-(-)-3-PLA alone did not reduce survival, suggesting that both L-(-)-3-PLA accumulation and the depletion of antioxidants contribute to reduced viability. Additionally, L-(-)-3-PLA directly suppressed intestinal permeability in C. elegans. In conclusion, the results of this study suggest that TJ may inhibit increased intestinal permeability through both rendering P. copri vulnerable and the direct effects of L-(-)-3-PLA. Further studies are needed to determine the relevance of these findings to humans.
针对人类的流行病学研究表明，食用番茄以及肠道微生物群中普雷沃氏菌、巨单胞菌和链球菌的组成比例与肠道通透性有关。在本研究中，我们使用秀丽隐杆线虫来研究这种因果关系。我们在普通培养基或含有1%（v/v）番茄汁的培养基（TJ培养基）中培养大肠杆菌OP50（秀丽隐杆线虫的标准食物）、普雷沃氏菌（P.）copri JCM 13464T、梭形巨单胞菌JCM 14723T和唾液链球菌JCM 5707T，将这些细菌喂食秀丽隐杆线虫三天，并用蓝精灵试验评估肠道通透性。在喂食于TJ培养基中培养的普雷沃氏菌的秀丽隐杆线虫中，蓝精灵个体的比例显著低于喂食于普通培养基中培养的相同细菌的线虫，而其他菌株未显示出这种培养基依赖性差异。有趣的是，在普通培养基中生长的热灭活普雷沃氏菌也降低了蓝精灵个体的比例。此外，在TJ培养基中生长的普雷沃氏菌接种到线虫生长培养基上后存活率较低，其他菌株未观察到这种效应。液相色谱 - 串联质谱分析表明，在TJ培养基中培养的普雷沃氏菌积累了L - (-) - 3 - 苯乳酸（L - (-) - 3 - PLA），该化合物因其通过氧化应激的抗菌特性及其对肠道屏障的保护作用而闻名。相比之下，已知抗氧化剂如2,3,4,9 - 四氢 - 1H - β - 咔啉 - 3 - 羧酸和环（苯丙氨酰 - 脯氨酰）的水平降低。仅在普通培养基中添加L - (-) - 3 - PLA培养普雷沃氏菌并不会降低存活率，这表明L - (-) - 3 - PLA的积累和抗氧化剂的消耗都导致了活力降低。此外，L - (-) - 3 - PLA直接抑制了秀丽隐杆线虫的肠道通透性。总之，本研究结果表明，TJ可能通过使普雷沃氏菌易受影响以及L - (-) - 3 - PLA的直接作用来抑制肠道通透性增加。需要进一步研究以确定这些发现与人类的相关性。
