常见于人类且通常被称为“非致病性”的单细胞肠道寄生虫的遗传多样性、宿主特异性及其公共卫生意义

IF 2.6 4区 医学 Q4 IMMUNOLOGY
Apmis Pub Date : 2025-09-09 DOI:10.1111/apm.70036
Christen Rune Stensvold
{"title":"常见于人类且通常被称为“非致病性”的单细胞肠道寄生虫的遗传多样性、宿主特异性及其公共卫生意义","authors":"Christen Rune Stensvold","doi":"10.1111/apm.70036","DOIUrl":null,"url":null,"abstract":"<p>Clinical microbiology involves the detection and differentiation of primarily bacteria, viruses, parasites and fungi in patients with infections. Billions of people may be colonised by one or more species of common luminal intestinal parasitic protists (CLIPPs) that are often detected in clinical microbiology laboratories; still, our knowledge on these organisms' impact on global health is very limited. The genera <i>Blastocystis</i>, <i>Dientamoeba</i>, <i>Entamoeba</i>, <i>Endolimax</i> and <i>Iodamoeba</i> comprise CLIPPs species, the life cycles of which, as opposed to single-celled pathogenic intestinal parasites (e.g., microsporidia and sporozoa), do probably not include gut-invasive stages that could result in pathological processes and thereby disease (except for <i>Entamoeba histolytica</i>). All five genera are parasites in the sense that they use a host to complete their life cycle; still, by many specialists, these are considered to be of limited clinical relevance and could possibly be referred to as ‘eukaryotic endobionts’ or even ‘endosymbionts’, in case they would have health-protective effects. The articles included in this thesis exemplify the work and the data that support the view that it might be more relevant to study these genera in a public health and gut ecology context than in a clinical microbiology context. Essential to investigating the impact of intestinal parasites on health and disease are accurate diagnostic tools, including DNA-based technology such as PCR and sequencing, plus accurate reference databases. Small subunit (SSU) ribosomal RNA (rRNA) genes consistently present in both pro- and eukaryotic organisms are today avidly used as taxonomic markers. DNA-based methods have been developed for genetic characterisation of microorganisms and provided data on species/subtypes/genotypes, etc. Metagenomics and metabarcoding (the use of low-specific PCR coupled with next-generation sequencing) can provide information on co-infection/co-colonisation with other organisms and enable screening for genetic diversity, even in complex matrices. By developing and implementing sensitive and specific DNA-based diagnostic tools and typing assays primarily based on the SSU rRNA gene, we have increased insight into the diversity, distribution and significance of CLIPPs. With these tools, we have shown that the genera <i>Blastocystis</i> and <i>Dientamoeba</i> are far more common than previously thought. Only 10–15 years ago, hypotheses on their distribution typically relied on data generated by traditional parasitological diagnostic methods, such as light microscopy. Hence, we have shown that most older children in Nigeria host <i>Blastocystis</i>, and that most children in day-care institutions in Denmark, if not all, get colonised by <i>Dientamoeba</i> at some point. Single-celled non-pathogenic intestinal parasites can be hosted by patients with diarrhoea and functional or inflammatory bowel diseases. However, emerging data appear to suggest that CLIPPs are generally more common in gut-healthy individuals than in patients with gastrointestinal symptoms. The research we have carried out on associations between CLIPPs and gut bacteria suggests that colonisation with these parasites is seen primarily in individuals with a healthy ‘gut flora’ (eubiosis). This observation should prompt future research projects focusing on the use of CLIPPs as biomarkers, and it should be investigated to which extent manipulation with CLIPPs could lead to changes in the gut flora and thereby be used as probiotics. In the event that it makes sense to speak of ‘infection’ by CLIPPs, we still lack tools to differentiate between colonisation and infection. We have known for decades that morphologically similar parasites can differ in terms of clinical impact and be genetically distinct, a feature that we refer to as ‘cryptic genetic diversity’. One example is <i>E. histolytica</i>, which cannot be differentiated from <i>Entamoeba dispar</i> by cyst morphological features. However, whereas <i>E. histolytica</i> can be invasive and give rise to amoebic dysentery and amoebiasis, <i>E. dispar</i> is by most specialists considered non-invasive and generally non-pathogenic. This insight led us to investigate genetic diversity among other species of <i>Entamoeba</i> as well as other CLIPPs genera. If we could demonstrate similar—or higher—degrees of diversity within <i>Blastocystis</i>, <i>Dientamoeba</i>, <i>Endolimax</i> and <i>Iodamoeba</i>, these differences might be key to explaining differences in parasite phenotype and thereby differences in the ability of the parasites to cause symptoms. Despite the disclosure of striking genetic diversity among some CLIPPs, we have found little support for such theories; however, more studies are needed. As for <i>Dientamoeba</i>, we have observed a more or less clonal expansion of one of the two genotypes known to exist, and this genotype appears to have global predominance. In contrast, extensive genetic diversity is observed between and within subtypes of <i>Blastocystis</i>: to date, more than 30 species, the so-called subtypes, have been acknowledged. We, and many others, have sought to identify whether one or more of these subtypes could be linked to the development of intestinal symptoms, but there is little evidence to support this hypothesis. We know that Subtypes 1–4 reflect about 95% of <i>Blastocystis</i> colonisation in humans, and we have shown that individuals with zoonotic subtypes (e.g., ST6, ST7 and ST8) might typically experience symptoms. We have disclosed astonishing genetic variation among other CLIPPs, which has led to the recognition of <i>Iodamoeba bütschlii</i>, <i>Endolimax nana, Entamoeba coli</i> and <i>Entamoeba hartmanni</i> as species complexes, where each species should be regarded as a complex of species (referred to as ‘subtypes’ or ‘ribosomal lineages’) with overlapping morphology. And where <i>E. histolytica</i> and <i>E. dispar</i> differ by only 1%–2% diversity across the SSU rRNA gene, we have observed up to at least 10% and 30% genetic difference among ribosomal lineages within <i>E. coli</i> and <i>I. bütschlii</i>, respectively, challenging species concepts currently applied. Our research has resulted in the recognition of three ribosomal lineages within both <i>E. coli</i> and <i>E. hartmanni</i>, as well as two ribosomal lineages of <i>E. nana</i> and <i>I. bütschlii</i>. Moreover, we have discovered a new lineage of <i>Entamoeba moshkovskii</i>. Molecular characterisation of intestinal parasites collected from different host species (humans, non-human primates, other mammals, birds, etc.) can help identify opportunity for transmission between human and non-human hosts. We have shown that pigs can host a few species/lineages that can readily colonise humans, such as <i>Entamoeba hartmanni</i> and <i>I. bütschlii</i>. Many other species of larger mammals are common hosts of <i>Blastocystis</i> and <i>Entamoeba</i>. However, for the two latter genera, the species/genetic variants observed in non-human hosts are typically different from those observed in humans, which could indicate that many species of CLIPPs have adapted to their respective hosts over a long period, resulting in relatively high host specificity. For <i>Blastocystis</i>, we have shown that even though a given subtype may be found in more than one host species, it is possible to demonstrate cryptic host specificity at allele level. For instance, even though both human and non-human primates can be colonised by ST3, host species-specific strains of ST3 circulate within these two host populations. With regards to <i>E. coli</i>, it is possible that ST1 has adapted to human hosts, while <i>E. coli</i> ST2 has adapted to a broader host range, including non-human primates and rodents. It has become clear that CLIPPs are common colonisers of the human background population, and even though we cannot disprove the existence of infection by any of these, it should be reasonable to consider clinical and medical intervention redundant in most cases. Perhaps it might even be so that one should try not to eradicate these organisms from the gut when first established. However, more studies are warranted to elucidate the significance of the pronounced genetic diversity observed in some CLIPPs with regards to transmission patterns and clinical significance. Future research in CLIPPs should also include studies that can elucidate those factors that favour colonisation with CLIPPs and what role CLIPPs have in host–gut ecology, metabolism and overall health condition. Finally, as human and non-human hosts share these parasitic genera, and as some protozoa possibly contribute to overall gut function in ruminants, it would be interesting to study these in domesticated and wild animals to learn more about the role of these parasites in health and disease, including investigations into whether some CLIPPs might be endosymbionts.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 9","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.70036","citationCount":"0","resultStr":"{\"title\":\"Aspects of Genetic Diversity, Host Specificity and Public Health Significance of Single-Celled Intestinal Parasites Commonly Observed in Humans and Mostly Referred to as ‘Non-Pathogenic’\",\"authors\":\"Christen Rune Stensvold\",\"doi\":\"10.1111/apm.70036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Clinical microbiology involves the detection and differentiation of primarily bacteria, viruses, parasites and fungi in patients with infections. Billions of people may be colonised by one or more species of common luminal intestinal parasitic protists (CLIPPs) that are often detected in clinical microbiology laboratories; still, our knowledge on these organisms' impact on global health is very limited. The genera <i>Blastocystis</i>, <i>Dientamoeba</i>, <i>Entamoeba</i>, <i>Endolimax</i> and <i>Iodamoeba</i> comprise CLIPPs species, the life cycles of which, as opposed to single-celled pathogenic intestinal parasites (e.g., microsporidia and sporozoa), do probably not include gut-invasive stages that could result in pathological processes and thereby disease (except for <i>Entamoeba histolytica</i>). All five genera are parasites in the sense that they use a host to complete their life cycle; still, by many specialists, these are considered to be of limited clinical relevance and could possibly be referred to as ‘eukaryotic endobionts’ or even ‘endosymbionts’, in case they would have health-protective effects. The articles included in this thesis exemplify the work and the data that support the view that it might be more relevant to study these genera in a public health and gut ecology context than in a clinical microbiology context. Essential to investigating the impact of intestinal parasites on health and disease are accurate diagnostic tools, including DNA-based technology such as PCR and sequencing, plus accurate reference databases. Small subunit (SSU) ribosomal RNA (rRNA) genes consistently present in both pro- and eukaryotic organisms are today avidly used as taxonomic markers. DNA-based methods have been developed for genetic characterisation of microorganisms and provided data on species/subtypes/genotypes, etc. Metagenomics and metabarcoding (the use of low-specific PCR coupled with next-generation sequencing) can provide information on co-infection/co-colonisation with other organisms and enable screening for genetic diversity, even in complex matrices. By developing and implementing sensitive and specific DNA-based diagnostic tools and typing assays primarily based on the SSU rRNA gene, we have increased insight into the diversity, distribution and significance of CLIPPs. With these tools, we have shown that the genera <i>Blastocystis</i> and <i>Dientamoeba</i> are far more common than previously thought. Only 10–15 years ago, hypotheses on their distribution typically relied on data generated by traditional parasitological diagnostic methods, such as light microscopy. Hence, we have shown that most older children in Nigeria host <i>Blastocystis</i>, and that most children in day-care institutions in Denmark, if not all, get colonised by <i>Dientamoeba</i> at some point. Single-celled non-pathogenic intestinal parasites can be hosted by patients with diarrhoea and functional or inflammatory bowel diseases. However, emerging data appear to suggest that CLIPPs are generally more common in gut-healthy individuals than in patients with gastrointestinal symptoms. The research we have carried out on associations between CLIPPs and gut bacteria suggests that colonisation with these parasites is seen primarily in individuals with a healthy ‘gut flora’ (eubiosis). This observation should prompt future research projects focusing on the use of CLIPPs as biomarkers, and it should be investigated to which extent manipulation with CLIPPs could lead to changes in the gut flora and thereby be used as probiotics. In the event that it makes sense to speak of ‘infection’ by CLIPPs, we still lack tools to differentiate between colonisation and infection. We have known for decades that morphologically similar parasites can differ in terms of clinical impact and be genetically distinct, a feature that we refer to as ‘cryptic genetic diversity’. One example is <i>E. histolytica</i>, which cannot be differentiated from <i>Entamoeba dispar</i> by cyst morphological features. However, whereas <i>E. histolytica</i> can be invasive and give rise to amoebic dysentery and amoebiasis, <i>E. dispar</i> is by most specialists considered non-invasive and generally non-pathogenic. This insight led us to investigate genetic diversity among other species of <i>Entamoeba</i> as well as other CLIPPs genera. If we could demonstrate similar—or higher—degrees of diversity within <i>Blastocystis</i>, <i>Dientamoeba</i>, <i>Endolimax</i> and <i>Iodamoeba</i>, these differences might be key to explaining differences in parasite phenotype and thereby differences in the ability of the parasites to cause symptoms. Despite the disclosure of striking genetic diversity among some CLIPPs, we have found little support for such theories; however, more studies are needed. As for <i>Dientamoeba</i>, we have observed a more or less clonal expansion of one of the two genotypes known to exist, and this genotype appears to have global predominance. In contrast, extensive genetic diversity is observed between and within subtypes of <i>Blastocystis</i>: to date, more than 30 species, the so-called subtypes, have been acknowledged. We, and many others, have sought to identify whether one or more of these subtypes could be linked to the development of intestinal symptoms, but there is little evidence to support this hypothesis. We know that Subtypes 1–4 reflect about 95% of <i>Blastocystis</i> colonisation in humans, and we have shown that individuals with zoonotic subtypes (e.g., ST6, ST7 and ST8) might typically experience symptoms. We have disclosed astonishing genetic variation among other CLIPPs, which has led to the recognition of <i>Iodamoeba bütschlii</i>, <i>Endolimax nana, Entamoeba coli</i> and <i>Entamoeba hartmanni</i> as species complexes, where each species should be regarded as a complex of species (referred to as ‘subtypes’ or ‘ribosomal lineages’) with overlapping morphology. And where <i>E. histolytica</i> and <i>E. dispar</i> differ by only 1%–2% diversity across the SSU rRNA gene, we have observed up to at least 10% and 30% genetic difference among ribosomal lineages within <i>E. coli</i> and <i>I. bütschlii</i>, respectively, challenging species concepts currently applied. Our research has resulted in the recognition of three ribosomal lineages within both <i>E. coli</i> and <i>E. hartmanni</i>, as well as two ribosomal lineages of <i>E. nana</i> and <i>I. bütschlii</i>. Moreover, we have discovered a new lineage of <i>Entamoeba moshkovskii</i>. Molecular characterisation of intestinal parasites collected from different host species (humans, non-human primates, other mammals, birds, etc.) can help identify opportunity for transmission between human and non-human hosts. We have shown that pigs can host a few species/lineages that can readily colonise humans, such as <i>Entamoeba hartmanni</i> and <i>I. bütschlii</i>. Many other species of larger mammals are common hosts of <i>Blastocystis</i> and <i>Entamoeba</i>. However, for the two latter genera, the species/genetic variants observed in non-human hosts are typically different from those observed in humans, which could indicate that many species of CLIPPs have adapted to their respective hosts over a long period, resulting in relatively high host specificity. For <i>Blastocystis</i>, we have shown that even though a given subtype may be found in more than one host species, it is possible to demonstrate cryptic host specificity at allele level. For instance, even though both human and non-human primates can be colonised by ST3, host species-specific strains of ST3 circulate within these two host populations. With regards to <i>E. coli</i>, it is possible that ST1 has adapted to human hosts, while <i>E. coli</i> ST2 has adapted to a broader host range, including non-human primates and rodents. It has become clear that CLIPPs are common colonisers of the human background population, and even though we cannot disprove the existence of infection by any of these, it should be reasonable to consider clinical and medical intervention redundant in most cases. Perhaps it might even be so that one should try not to eradicate these organisms from the gut when first established. However, more studies are warranted to elucidate the significance of the pronounced genetic diversity observed in some CLIPPs with regards to transmission patterns and clinical significance. Future research in CLIPPs should also include studies that can elucidate those factors that favour colonisation with CLIPPs and what role CLIPPs have in host–gut ecology, metabolism and overall health condition. Finally, as human and non-human hosts share these parasitic genera, and as some protozoa possibly contribute to overall gut function in ruminants, it would be interesting to study these in domesticated and wild animals to learn more about the role of these parasites in health and disease, including investigations into whether some CLIPPs might be endosymbionts.</p>\",\"PeriodicalId\":8167,\"journal\":{\"name\":\"Apmis\",\"volume\":\"133 9\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.70036\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Apmis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/apm.70036\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Apmis","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/apm.70036","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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摘要

临床微生物学主要是对感染患者体内的细菌、病毒、寄生虫和真菌进行检测和鉴别。数十亿人可能被一种或多种常见的肠道寄生原生生物(CLIPPs)定植,这些生物通常在临床微生物实验室中检测到;尽管如此,我们对这些生物对全球健康的影响的了解非常有限。Blastocystis、Dientamoeba、Entamoeba、Endolimax和Iodamoeba属包括CLIPPs物种,其生命周期与单细胞致病性肠道寄生虫(如微孢子虫和孢子虫)相反,可能不包括可能导致病理过程并因此导致疾病的肠道侵入阶段(溶组织内阿米巴除外)。这五个属都是寄生虫,因为它们依靠宿主来完成它们的生命周期;然而,许多专家认为,这些生物的临床意义有限,如果它们具有保护健康的作用,可能被称为“真核内生生物”或甚至“内生共生生物”。本论文中包含的文章举例说明了支持这一观点的工作和数据,即在公共卫生和肠道生态学背景下研究这些属可能比在临床微生物学背景下更相关。调查肠道寄生虫对健康和疾病的影响至关重要的是准确的诊断工具,包括PCR和测序等基于dna的技术,以及准确的参考数据库。小亚单位(SSU)核糖体RNA (rRNA)基因一致存在于原核生物和真核生物中,目前被广泛用作分类标记。基于dna的方法已被开发用于微生物的遗传特征,并提供了物种/亚型/基因型等数据。宏基因组学和元条形码(使用低特异性PCR与下一代测序相结合)可以提供与其他生物体共感染/共定植的信息,并能够筛选遗传多样性,即使在复杂的基质中也是如此。通过开发和实施敏感和特异性的基于dna的诊断工具和主要基于SSU rRNA基因的分型分析,我们对CLIPPs的多样性、分布和意义有了更深入的了解。有了这些工具,我们已经表明囊虫属和地阿米巴属比以前认为的要普遍得多。仅在10-15年前,关于它们分布的假设通常依赖于光显微镜等传统寄生虫学诊断方法产生的数据。因此,我们已经表明,尼日利亚的大多数大一点的儿童都有囊虫,丹麦日托机构的大多数儿童,如果不是全部,在某个时候都会被地entamoeba所感染。单细胞非致病性肠道寄生虫可由腹泻和功能性或炎症性肠病患者感染。然而,新出现的数据似乎表明,在肠道健康的个体中,CLIPPs通常比在有胃肠道症状的患者中更常见。我们对CLIPPs和肠道细菌之间的关系进行的研究表明,这些寄生虫的定植主要见于具有健康肠道菌群(益生菌)的个体。这一观察结果应该促使未来的研究项目关注CLIPPs作为生物标志物的使用,并且应该研究CLIPPs的操作在多大程度上可能导致肠道菌群的变化,从而被用作益生菌。即使通过CLIPPs说“感染”是有意义的,我们仍然缺乏区分定植和感染的工具。几十年来,我们已经知道,形态相似的寄生虫在临床影响方面可能不同,并且在遗传上不同,我们将这种特征称为“隐性遗传多样性”。一个例子是溶组织芽胞杆菌,它不能从囊肿的形态特征与异内阿米巴原虫区分开。然而,尽管溶组织芽胞杆菌可能是侵入性的,并引起阿米巴痢疾和阿米巴病,但大多数专家认为异芽胞杆菌是非侵入性的,通常是非致病性的。这一见解使我们研究了其他种类的内阿米巴原虫以及其他CLIPPs属的遗传多样性。如果我们能证明囊虫、地阿米巴、内多利莫巴和碘达米巴之间存在类似或更高程度的多样性,这些差异可能是解释寄生虫表型差异的关键,从而解释寄生虫引起症状的能力差异。尽管在一些clipp中发现了惊人的遗传多样性,但我们发现很少有证据支持这些理论;然而,还需要更多的研究。对于地entamoeba,我们已经观察到已知存在的两种基因型中的一种或多或少的克隆扩增,并且该基因型似乎具有全球优势。 相比之下,在囊虫亚型之间和内部观察到广泛的遗传多样性:迄今为止,已经确认了30多种所谓的亚型。我们和其他许多人都试图确定这些亚型中的一种或多种是否与肠道症状的发展有关,但几乎没有证据支持这一假设。我们知道1-4亚型反映了大约95%的囊虫在人类中的定植,并且我们已经表明具有人畜共患亚型(例如ST6、ST7和ST8)的个体可能通常会出现症状。我们已经揭示了其他CLIPPs中惊人的遗传变异,这导致了对Iodamoeba btschlii, Endolimax nana, Entamoeba coli和Entamoeba hartmanni作为物种复合体的认识,其中每个物种都应被视为具有重叠形态的物种复合体(称为“亚型”或“核糖体谱系”)。在溶组织芽胞杆菌和异丝芽胞杆菌在SSU rRNA基因上的多样性差异仅为1%-2%的地方,我们已经观察到大肠杆菌和大肠杆菌的核糖体谱系之间分别存在至少10%和30%的遗传差异,这对目前应用的物种概念提出了挑战。我们的研究结果已经在大肠杆菌和大肠杆菌中识别出三个核糖体谱系,以及在大肠杆菌和大肠杆菌中识别出两个核糖体谱系。此外,我们还发现了一个新的莫什科夫斯基内阿米巴谱系。从不同宿主物种(人类、非人灵长类动物、其他哺乳动物、鸟类等)收集的肠道寄生虫的分子特征可以帮助确定人类和非人宿主之间传播的机会。我们已经证明,猪可以携带一些物种/谱系,这些物种/谱系可以很容易地在人类中定居,例如哈特曼内阿米巴和I. b<s:1> tschlii。许多其他种类的大型哺乳动物是囊虫和内阿米巴原虫的常见宿主。然而,对于后两属,在非人类宿主中观察到的物种/遗传变异通常与在人类中观察到的物种/遗传变异不同,这可能表明许多CLIPPs物种在很长一段时间内已经适应了各自的宿主,从而导致相对较高的宿主特异性。对于囊虫,我们已经证明,即使一个给定的亚型可能在多个宿主物种中发现,也有可能在等位基因水平上证明隐宿主特异性。例如,尽管人类和非人类灵长类动物都可以被ST3定植,但宿主物种特有的ST3菌株在这两个宿主种群中传播。关于大肠杆菌,有可能ST1已经适应了人类宿主,而大肠杆菌ST2已经适应了更广泛的宿主范围,包括非人灵长类动物和啮齿动物。很明显,CLIPPs是人类背景人群的常见殖民者,尽管我们不能通过任何这些来反驳感染的存在,但在大多数情况下,认为临床和医疗干预是多余的应该是合理的。甚至可能是这样,当这些有机体刚建立时,人们应该尽量不要从肠道中消灭它们。然而,需要更多的研究来阐明在一些CLIPPs中观察到的显著遗传多样性在传播模式和临床意义方面的重要性。未来对CLIPPs的研究还应该包括能够阐明那些有利于CLIPPs定植的因素以及CLIPPs在宿主肠道生态、代谢和整体健康状况中的作用的研究。最后,由于人类和非人类宿主共享这些寄生属,并且一些原生动物可能对反刍动物的整体肠道功能有贡献,因此在驯养和野生动物中研究这些寄生虫,以了解更多关于这些寄生虫在健康和疾病中的作用,包括调查一些CLIPPs是否可能是内共生体,将是一件有趣的事情。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Aspects of Genetic Diversity, Host Specificity and Public Health Significance of Single-Celled Intestinal Parasites Commonly Observed in Humans and Mostly Referred to as ‘Non-Pathogenic’

Aspects of Genetic Diversity, Host Specificity and Public Health Significance of Single-Celled Intestinal Parasites Commonly Observed in Humans and Mostly Referred to as ‘Non-Pathogenic’

Clinical microbiology involves the detection and differentiation of primarily bacteria, viruses, parasites and fungi in patients with infections. Billions of people may be colonised by one or more species of common luminal intestinal parasitic protists (CLIPPs) that are often detected in clinical microbiology laboratories; still, our knowledge on these organisms' impact on global health is very limited. The genera Blastocystis, Dientamoeba, Entamoeba, Endolimax and Iodamoeba comprise CLIPPs species, the life cycles of which, as opposed to single-celled pathogenic intestinal parasites (e.g., microsporidia and sporozoa), do probably not include gut-invasive stages that could result in pathological processes and thereby disease (except for Entamoeba histolytica). All five genera are parasites in the sense that they use a host to complete their life cycle; still, by many specialists, these are considered to be of limited clinical relevance and could possibly be referred to as ‘eukaryotic endobionts’ or even ‘endosymbionts’, in case they would have health-protective effects. The articles included in this thesis exemplify the work and the data that support the view that it might be more relevant to study these genera in a public health and gut ecology context than in a clinical microbiology context. Essential to investigating the impact of intestinal parasites on health and disease are accurate diagnostic tools, including DNA-based technology such as PCR and sequencing, plus accurate reference databases. Small subunit (SSU) ribosomal RNA (rRNA) genes consistently present in both pro- and eukaryotic organisms are today avidly used as taxonomic markers. DNA-based methods have been developed for genetic characterisation of microorganisms and provided data on species/subtypes/genotypes, etc. Metagenomics and metabarcoding (the use of low-specific PCR coupled with next-generation sequencing) can provide information on co-infection/co-colonisation with other organisms and enable screening for genetic diversity, even in complex matrices. By developing and implementing sensitive and specific DNA-based diagnostic tools and typing assays primarily based on the SSU rRNA gene, we have increased insight into the diversity, distribution and significance of CLIPPs. With these tools, we have shown that the genera Blastocystis and Dientamoeba are far more common than previously thought. Only 10–15 years ago, hypotheses on their distribution typically relied on data generated by traditional parasitological diagnostic methods, such as light microscopy. Hence, we have shown that most older children in Nigeria host Blastocystis, and that most children in day-care institutions in Denmark, if not all, get colonised by Dientamoeba at some point. Single-celled non-pathogenic intestinal parasites can be hosted by patients with diarrhoea and functional or inflammatory bowel diseases. However, emerging data appear to suggest that CLIPPs are generally more common in gut-healthy individuals than in patients with gastrointestinal symptoms. The research we have carried out on associations between CLIPPs and gut bacteria suggests that colonisation with these parasites is seen primarily in individuals with a healthy ‘gut flora’ (eubiosis). This observation should prompt future research projects focusing on the use of CLIPPs as biomarkers, and it should be investigated to which extent manipulation with CLIPPs could lead to changes in the gut flora and thereby be used as probiotics. In the event that it makes sense to speak of ‘infection’ by CLIPPs, we still lack tools to differentiate between colonisation and infection. We have known for decades that morphologically similar parasites can differ in terms of clinical impact and be genetically distinct, a feature that we refer to as ‘cryptic genetic diversity’. One example is E. histolytica, which cannot be differentiated from Entamoeba dispar by cyst morphological features. However, whereas E. histolytica can be invasive and give rise to amoebic dysentery and amoebiasis, E. dispar is by most specialists considered non-invasive and generally non-pathogenic. This insight led us to investigate genetic diversity among other species of Entamoeba as well as other CLIPPs genera. If we could demonstrate similar—or higher—degrees of diversity within Blastocystis, Dientamoeba, Endolimax and Iodamoeba, these differences might be key to explaining differences in parasite phenotype and thereby differences in the ability of the parasites to cause symptoms. Despite the disclosure of striking genetic diversity among some CLIPPs, we have found little support for such theories; however, more studies are needed. As for Dientamoeba, we have observed a more or less clonal expansion of one of the two genotypes known to exist, and this genotype appears to have global predominance. In contrast, extensive genetic diversity is observed between and within subtypes of Blastocystis: to date, more than 30 species, the so-called subtypes, have been acknowledged. We, and many others, have sought to identify whether one or more of these subtypes could be linked to the development of intestinal symptoms, but there is little evidence to support this hypothesis. We know that Subtypes 1–4 reflect about 95% of Blastocystis colonisation in humans, and we have shown that individuals with zoonotic subtypes (e.g., ST6, ST7 and ST8) might typically experience symptoms. We have disclosed astonishing genetic variation among other CLIPPs, which has led to the recognition of Iodamoeba bütschlii, Endolimax nana, Entamoeba coli and Entamoeba hartmanni as species complexes, where each species should be regarded as a complex of species (referred to as ‘subtypes’ or ‘ribosomal lineages’) with overlapping morphology. And where E. histolytica and E. dispar differ by only 1%–2% diversity across the SSU rRNA gene, we have observed up to at least 10% and 30% genetic difference among ribosomal lineages within E. coli and I. bütschlii, respectively, challenging species concepts currently applied. Our research has resulted in the recognition of three ribosomal lineages within both E. coli and E. hartmanni, as well as two ribosomal lineages of E. nana and I. bütschlii. Moreover, we have discovered a new lineage of Entamoeba moshkovskii. Molecular characterisation of intestinal parasites collected from different host species (humans, non-human primates, other mammals, birds, etc.) can help identify opportunity for transmission between human and non-human hosts. We have shown that pigs can host a few species/lineages that can readily colonise humans, such as Entamoeba hartmanni and I. bütschlii. Many other species of larger mammals are common hosts of Blastocystis and Entamoeba. However, for the two latter genera, the species/genetic variants observed in non-human hosts are typically different from those observed in humans, which could indicate that many species of CLIPPs have adapted to their respective hosts over a long period, resulting in relatively high host specificity. For Blastocystis, we have shown that even though a given subtype may be found in more than one host species, it is possible to demonstrate cryptic host specificity at allele level. For instance, even though both human and non-human primates can be colonised by ST3, host species-specific strains of ST3 circulate within these two host populations. With regards to E. coli, it is possible that ST1 has adapted to human hosts, while E. coli ST2 has adapted to a broader host range, including non-human primates and rodents. It has become clear that CLIPPs are common colonisers of the human background population, and even though we cannot disprove the existence of infection by any of these, it should be reasonable to consider clinical and medical intervention redundant in most cases. Perhaps it might even be so that one should try not to eradicate these organisms from the gut when first established. However, more studies are warranted to elucidate the significance of the pronounced genetic diversity observed in some CLIPPs with regards to transmission patterns and clinical significance. Future research in CLIPPs should also include studies that can elucidate those factors that favour colonisation with CLIPPs and what role CLIPPs have in host–gut ecology, metabolism and overall health condition. Finally, as human and non-human hosts share these parasitic genera, and as some protozoa possibly contribute to overall gut function in ruminants, it would be interesting to study these in domesticated and wild animals to learn more about the role of these parasites in health and disease, including investigations into whether some CLIPPs might be endosymbionts.

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来源期刊
Apmis
Apmis 医学-病理学
CiteScore
5.20
自引率
0.00%
发文量
91
审稿时长
2 months
期刊介绍: APMIS, formerly Acta Pathologica, Microbiologica et Immunologica Scandinavica, has been published since 1924 by the Scandinavian Societies for Medical Microbiology and Pathology as a non-profit-making scientific journal.
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