Goudy Steven L, Bradley Heath, Gacasan Camillo Anthony, Toma Afra, Naudin Crystal R, Wuest William M, Tomov Martin, Serpooshan Vahid, Coskun Ahmet, Jones Rheinallt M
bioRxiv. 2023 Jun 6:2023.06.02.543508. doi: 10.1101/2023.06.02.543508.
The oral microbiome is a complex community that matures with dental development while oral health is also a recognized risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge that is further complicated by a connection of the oral and nasal microbiome. In this study, we characterized the changes in the oral microbiome of mice following a freshly inflicted wound in the oral palate that results in an open and unhealed ONF. Creation of an ONF in mice significantly lowered oral microbiome alpha diversity, with concurrent blooms of in the oral cavity. Treatment of mice with oral antibiotics one week prior to ONF infliction resulted in a reduction in the alpha diversity, prevented and blooms, but did not impact ONF healing. Strikingly, delivery of the beneficial microbe subsp. cremoris (LLC) to the wound bed of the freshly inflicted ONF via a PEG-MAL hydrogel vehicle resulted in rapid healing of the ONF. Healing of the ONF was associated with the maintenance of relatively high microbiome alpha diversity, and limited the abundance of and in the oral cavity. These data demonstrate that a freshly inflicted ONF in the murine palate is associated with a dysbiotic oral microbiome state that may prevent ONF healing, and a bloom of opportunistic pathogens. The data also demonstrate that delivery of a specific beneficial microbe, LLC, to the ONF can boost wound healing, can restore and/or preserve oral microbiome diversity, and inhibit blooms of opportunistic pathogens.
口腔微生物群是一个复杂的群落，它随着牙齿发育而成熟，同时口腔健康也是公认的全身性疾病风险因素。尽管口腔中存在大量微生物负荷，但口腔浅表伤口愈合迅速且几乎不留疤痕。相比之下，口鼻瘘（ONF）的形成，通常发生在腭裂修复手术后，是一个重大的伤口愈合挑战，口腔和鼻腔微生物群的连通使其进一步复杂化。在本研究中，我们对小鼠口腔腭部新造成伤口导致开放性且未愈合的ONF后口腔微生物群的变化进行了表征。在小鼠中创建ONF显著降低了口腔微生物群的α多样性，同时口腔中 大量繁殖。在造成ONF前一周用口服抗生素治疗小鼠，导致α多样性降低，防止了 和 的大量繁殖，但并未影响ONF愈合。令人惊讶的是，通过聚乙二醇 - 马来酰亚胺（PEG - MAL）水凝胶载体将有益微生物 亚种cremoris（LLC）递送至新造成的ONF伤口床，导致ONF迅速愈合。ONF的愈合与维持相对较高的微生物群α多样性相关，并限制了口腔中 和 的丰度。这些数据表明，小鼠腭部新造成的ONF与可能阻碍ONF愈合的失调口腔微生物群状态以及机会性病原体的大量繁殖有关。数据还表明，将特定的有益微生物LLC递送至ONF可以促进伤口愈合，恢复和/或保持口腔微生物群多样性，并抑制机会性病原体的大量繁殖。
