Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.
Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.
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DOI：
10.1371/journal.pone.0248322
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Jeffries MA
中科院分区：
文献类型：
--
作者：
Velasco C;Dunn C;Sturdy C;Izda V;Martin J;Rivas A;McNaughton J;Jeffries MA
成人弹性软骨修复能力有限。相比之下，MRL/MPJ(MRL)小鼠能够自发愈合耳朵穿孔。这项研究被用来描述治愈和非治愈小鼠之间的微生物组差异，并评估这种愈合表型是否可以通过肠道微生物组移植来转移。我们将断奶时和成年时口服MRL/MPJ盲肠内容物的C57BL/6J(B6)小鼠(n=57)，在2.0 mm冲头后4周测量耳洞闭合率，并与赋形剂移植的MRL和B6(n=25)和B6移植的MRL(n=20)小鼠进行比较。评估了性别效应、相对于耳洞的移植时机和跨代遗传力。在一个子集(n=58)中，盲肠微生物群通过16S测序进行了描述，并与耳孔闭合进行了比较。利用PICRUST对微生物元基因组进行鉴定。无论是在断奶小鼠还是成年小鼠身上，将MRL微生物群移植到B6小鼠身上，改善了耳洞的闭合。B6-Vehicle组小鼠耳洞愈合较差(0.25±0.03 mm，2 mm耳洞4周后愈合[2.0 mm-最终耳洞大小]，均值±扫描电子显微镜)，而MRL-Vehicle组小鼠耳洞愈合良好(1.4±0.1 mm)。移植MRL的B6小鼠的愈合速度约为B6-Vehicle小鼠的三倍，是MRL-Vehicle小鼠的一半(0.74±0.05 mm，P=6.9E-10 vs.B6-Vehicle，P=5.2E-12 vs.MRL-Vehicle)。用B6盲肠材料移植MRL小鼠并不影响MRL愈合(B6移植MRL 1.3±0.1 vs.MRL-Vehicle 1.4±0.1，p=0.36)。在耳洞打孔之前进行移植与最大程度的耳洞闭合有关。移植小鼠的子代愈合情况明显好于未移植的对照组小鼠(子代：0.63±0.03 mm，平均扫描电子显微镜：0.25±0.03 mm，对照组：0.25±0.03 mm，n=39，P=4.6E-11)。几个微生物支系与愈合相关，包括菲米库特(R=0.84，P=8.0E-7)、乳杆菌(R=0.65，P=1.1E-3)和韦氏杆菌(R=-0.80，P=9.2E-6)。各组女性愈合情况均优于男性(B6移植组P=0.059，移植组P=0.096，移植组后代P=0.0038，移植组P=1.6E-6，移植组P=0.0031)。雌性小鼠盲肠微生物区系相对于雄性小鼠的许多分支特征与MRL和移植MRL的B6小鼠与B6对照组小鼠的特征分支相同，包括雌性小鼠的梭状芽胞杆菌增加和雌性小鼠的韦氏杆菌减少。在这项研究中，我们在MRL小鼠中发现了微生物群和组织再生之间的联系，并证明了这种特征可以通过微生物群移植转移到未痊愈的小鼠身上。我们确定了几个与愈合相关的微生物支系。
Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation. We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt. Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm—final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice. In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.
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影响因子：
4.3
作者：
Gupta, Asheesh;Kumar, Ratan;Sawhney, Ramesh C.
通讯作者：
Sawhney, Ramesh C.
影响因子：
16.6
作者：
Boer, Cindy G.;Radjabzadeh, Djawad;van Meurs, Joyce B. J.
通讯作者：
van Meurs, Joyce B. J.
影响因子：
2.9
作者：
Chadwick, Robert B.;Bu, Liming;Baylink, David J.
通讯作者：
Baylink, David J.
影响因子：
2.4
作者：
Buckley, Gemma;Metcalfe, Anthony D.;Ferguson, Mark W. J.
通讯作者：
Ferguson, Mark W. J.
DOI：
10.1073/pnas.90.5.1756
发表时间：
1993-03-01
影响因子：
11.1
作者：
ADACHI, M;WATANABEFUKUNAGA, R;NAGATA, S
通讯作者：
NAGATA, S