Etienne-Mesmin Lucie, Meslier Victoria, Uriot Ophélie, Fournier Elora, Deschamps Charlotte, Denis Sylvain, David Aymeric, Jegou Sarah, Morabito Christian, Quinquis Benoit, Thirion Florence, Plaza Oñate Florian, Le Chatelier Emmanuelle, Ehrlich S Dusko, Blanquet-Diot Stéphanie, Almeida Mathieu
UMR 454 UCA-INRAE Microbiologie Environnement DIgestif et Santé (MEDIS), Université Clermont Auvergne, Clermont-Ferrand, France.
Université Paris-Saclay, INRAE, MetaGenoPolis (MGP), Jouy-en-Josas, France.
Microbiol Spectr. 2023 Mar 27;11(2):e0434422. doi: 10.1128/spectrum.04344-22.
Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and the host. In this proof-of-concept study, we proposed a new model of oral-to-gut invasion by the combined use of an model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in the colon model inoculated with a fecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, while species richness levels decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes. Here, we propose a new model of oral-to-gut invasion by the combined use of an model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Our study revealed the importance of integrating the mucus compartment, which retained higher microbial richness during fermentation, showed the preference of oral microbial invaders for the mucosal resources, and indicated potential oral-to-intestinal mucosal competitions. It also underlined promising opportunities to further understand mechanisms of oral invasion into the human gut microbiome, define microbe-microbe and mucus-microbe interactions in a compartmentalized fashion, and help to better characterize the potential of oral microbial invasion and their persistence in the gut.
人类微生物组特征研究的最新进展揭示，在肠道生态失调患者的粪便中可检测到大量口腔微生物。然而，对于这些侵入性口腔微生物与肠道共生微生物群及宿主之间的潜在相互作用，我们却知之甚少。在这项概念验证研究中，我们通过联合使用一种模拟人类结肠物理化学和微生物（管腔及黏液相关微生物）参数的模型（M-ARCOL）、一种唾液富集方案以及全基因组鸟枪法测序，提出了一种口腔至肠道侵袭的新模型。通过将富集后的唾液注入接种了来自同一位健康成年供体粪便样本的结肠模型中，模拟口腔微生物对肠道微生物群的侵袭。随着时间推移，M-ARCOL的黏膜区能够保持最高的物种丰富度水平，而管腔区的物种丰富度水平则有所下降。这项研究还表明，口腔微生物更倾向于在黏膜微环境中定殖，提示了潜在的口腔至肠道黏膜竞争。这种口腔至肠道侵袭的新模型能够为口腔微生物群在各种疾病过程中的作用提供有用的机制性见解。在此，我们通过联合使用一种模拟人类结肠物理化学和微生物（管腔及黏液相关微生物）参数的模型（M-ARCOL）、一种唾液富集方案以及全基因组鸟枪法测序，提出了一种口腔至肠道侵袭的新模型。我们的研究揭示了整合黏液区的重要性，该区域在发酵过程中保持了较高的微生物丰富度，显示了口腔微生物入侵者对黏膜资源的偏好，并表明了潜在的口腔至肠道黏膜竞争。它还强调了一些有前景的机会，可进一步了解口腔侵入人类肠道微生物群的机制，以分区方式定义微生物-微生物和黏液-微生物相互作用，并有助于更好地描述口腔微生物侵袭的潜力及其在肠道中的持久性。
