Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.

Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.
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DOI:
10.1128/spectrum.01554-23
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发表时间:
2023-12-12
影响因子:
3.7
通讯作者:
Schmidt, Nathan W.
Schmidt, Nathan W.
中科院分区:
生物学1区
文献类型:
--
作者:
Van Den Ham, Kristin M.;Little, Morgan R.;Bednarski, Olivia J.;Fusco, Elizabeth M.;Mandal, Rabindra K.;Mitra, Riten;Li, Shanping;Doumbo, Safiatou;Doumtabe, Didier;Kayentao, Kassoum;Ongoiba, Aissata;Traore, Boubacar;Crompton, Peter D.;Schmidt, Nathan W.

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肠道微生物群越来越被认为是许多疾病病因学中的一个重要因素,也是对各种治疗的免疫反应的一个潜在决定因素。最近的研究表明,低收入和中等收入国家对疫苗接种的次优免疫原性反应可能与肠道微生物组的差异有关,而肠道微生物组在西方国家和非西方国家之间存在很大差异。然而,对非西方微生物组的特征及其与健康和免疫的关系的考虑不足。人源化小鼠模型已被用于更好地了解肠道微生物群与健康结果之间的因果关系,但在很大程度上仅限于对西方微生物群的研究。因此,我们感兴趣的是确定用于将带有西方微生物群的无菌小鼠人源化的灌胃策略是否适用于将带有非洲农村粪便样本的无菌小鼠人源化。在这里,我们评估了灌胃次数和频率的影响,以及供体匹配饮食对无菌小鼠马里粪便微生物群定植的影响。一次灌胃不足以提供稳定的马里微生物群,而四次每周灌胃导致更一致的人类供体类群定植。有趣的是,与固定配方的以谷物为基础的小鼠食物相比,与供体匹配的饮食并没有改善定植。随后使用非洲肠道微生物群人源化非生物小鼠模型进行表型研究,将有助于更好地了解非洲肠道微生物群与健康之间的相互作用,并可能有助于开发针对非西方人群微生物群依赖性疾病的改进治疗方法。越来越多的证据表明,肠道内的微生物(肠道菌群)对人类的健康起着重要作用。然而,由于可能导致疾病的各种内部和环境因素的复杂性,在确定肠道微生物群在人类疾病中的具体作用方面存在相当大的挑战。缺乏所有微生物的小鼠(无菌小鼠)可以用人类粪便样本定殖,以检查肠道微生物群对疾病的特定贡献。这些方法主要集中在从西方国家个人获得的粪便样本上。因此,对于用西方人的粪便定殖无菌小鼠的方法是否适用于用非西方人的粪便定殖无菌小鼠,人们的理解是有限的。在这里,我们报告了用马里儿童粪便样本定殖无菌小鼠的结果。
Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.
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发表时间: 2015-11-11
影响因子: 30.3
作者:
Johansson ME;Jakobsson HE;Holmén-Larsson J;Schütte A;Ermund A;Rodríguez-Piñeiro AM;Arike L;Wising C;Svensson F;Bäckhed F;Hansson GC
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DOI: 10.1038/nature02285
发表时间: 2004-01-29
期刊: NATURE
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影响因子: 11.1
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