铁、宿主和肠道菌群相互作用的研究进展

目的 研究铁、宿主和肠道菌群之间的相互关系及其对肠道健康的影响。方法 检索中国知网、PubMed、EMBASE、Web of Science等数据库,查找铁和肠道菌群的相关文献,并进行整理归纳与总结。结果 铁对于维持宿主健康和肠道微生物生长定植具有重要作用,同时肠道微生物也影响着宿主铁的吸收利用。在一些病理条件下,肠道内未被吸收的铁可与微生物及其代谢物相互作用对宿主形成一种致病关系。结论 避免缺铁和铁过量引起的肠道菌群失调及其可能导致的宿主健康损害和疾病风险,并制订特殊生理状态和疾病状态下补充铁的策略,是目前医务工作者需要重新思考的问题。     

阴道微生物在宫颈癌中作用机制的研究进展

宫颈癌是妇产科最常见的恶性肿瘤,在2018年全球女性恶性肿瘤数据统计中,宫颈癌的发病率和死亡率处于第4位,有关宫颈癌的研究一直是妇产科学者关注的热点。近年随着微生物组学的展开,阴道微生物群的组成和变动与人乳头瘤病毒（HPV）的侵袭、持续感染及宫颈癌的相关性探讨逐步增多。乳酸杆菌在正常宫颈阴道菌群中占据主导地位,其可以维持阴道微生态的平衡、抑制病原微生物生长以及增强阴道的局部抗感染和抗肿瘤能力,有望成为未来治疗宫颈癌的新策略。目前研究表明,阴道微生物群的异常变化与宫颈癌发生发展有一定的关联,有些阴道细菌通过不同的机制直接或间接发挥作用。就阴道微生物群的抗癌作用机制及其应用于宫颈癌的潜力进行综述。     

Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.     

Familial adenomatous polyposis and changes in the gut microbiota: New insights into colorectal cancer carcinogenesis

Patients with familial adenomatous polyposis (FAP), an autosomal dominant hereditary colorectal cancer syndrome, have a lifetime risk of developing cancer of nearly 100%. Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer. Some gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, Clostridium difficile, Peptostreptococcus, and enterotoxigenic Bacteroides fragilis, could be implicated in colorectal carcinogenesis through different mechanisms, including the maintenance of a chronic inflammatory state, production of bioactive tumorigenic metabolites, and DNA damage. Studies using the adenomatous polyposis coli^Min/+ mouse model, which resembles FAP in most respects, have shown that specific changes in the intestinal microbial community could influence a multistep progression, the intestinal “adenoma-carcinoma sequence”, which involves mucosal barrier injury, low-grade inflammation, activation of the Wnt pathway. Therefore, modulation of gut microbiota might represent a novel therapeutic target for patients with FAP. Administration of probiotics, prebiotics, antibiotics, and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP. The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.     

Adaptive immune education by gut microbiota antigens

Host–microbiota mutualism has been established during long‐term co‐evolution. A diverse and rich gut microbiota plays an essential role in the development and maturation of the host immune system. Education of the adaptive immune compartment by gut microbiota antigens is important in establishing immune balance. In particular, a critical time frame immediately after birth provides a ‘window of opportunity’ for the development of lymphoid structures, differentiation and maturation of T and B cells and, most importantly, establishment of immune tolerance to gut commensals. Depending on the colonization niche, antigen type and metabolic property of different gut microbes, CD4 T‐cell responses vary greatly, which results in differentiation into distinct subsets. As a consequence, certain bacteria elicit effector‐like immune responses by promoting the production of pro‐inflammatory cytokines such as interferon‐γ and interleukin‐17A, whereas other bacteria favour the generation of regulatory CD4 T cells and provide help with gut homeostasis. The microbiota have profound effects on B cells also. Gut microbial exposure leads to a continuous diversification of B‐cell repertoire and the production of T‐dependent and ‐independent antibodies, especially IgA. These combined effects of the gut microbes provide an elegant educational process to the adaptive immune network. Contrariwise, failure of this process results in a reduced homeostasis with the gut microbiota, and an increased susceptibility to various immune disorders, both inside and outside the gut. With more definitive microbial–immune relations waiting to be discovered, modulation of the host gut microbiota has a promising future for disease intervention.     

Contributions of the intestinal microbiome in lung immunity

The intestine is a critical site of immune cell development that not only controls intestinal immunity but extra‐intestinal immunity as well. Recent findings have highlighted important roles for gut microbiota in shaping lung inflammation. Here, we discuss interactions between the microbiota and immune system including T cells, protective effects of microbiota on lung infections, the role of diet in shaping the composition of gut microbiota and susceptibility to asthma, epidemiologic evidence implicating antibiotic use and microbiota in asthma and clinical trials investigating probiotics as potential treatments for atopy and asthma. The systemic effects of gut microbiota are partially attributed to their generating metabolites including short chain fatty acids, which can suppress lung inflammation through the activation of G protein‐coupled receptors. Thus, studying the interactions between microbiota and immune cells can lead to the identification of therapeutic targets for chronic lower respiratory diseases.     

Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice

ABSTRACT

The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr^?/- ) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemic Ldlr^?/- mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GF Ldlr^?/- mice had altered inflammatory plasma protein markers and reduced smooth muscle cell content in their atherosclerotic root plaques relative to CONV-R Ldlr^?/- mice. Neither absolute nor relative aortic root or aortic arch plaque size correlated with age. Our analyses on GF Ldlr^?/- mice did not reveal a significant contribution of the microbiota in late aortic atherosclerosis.     

The microbiota revolution: Excitement and caution

Scientific progress is characterized by important technological advances. Next‐generation DNA sequencing has, in the past few years, led to a major scientific revolution: the microbiome revolution. It has become possible to generate a fingerprint of the whole microbiota of any given environment. As it becomes clear that the microbiota affects several aspects of our lives, each new scientific finding should ideally be analyzed in light of these communities. For instance, animal experimentation should consider animal sources and husbandry; human experimentation should include analysis of microenvironmental cues that might affect the microbiota, including diet, antibiotic, and drug use, genetics. When analyzing the activity of a drug, we should remember that, according to the microbiota of the host, different drug activities might be observed, either due to modification or degradation by the microbiota, or because the microbiota changes the immune system of the host in a way that makes that drug more or less effective. This minireview will not be a comprehensive review on the interaction between the host and microbiota, but it will aim at creating awareness on why we should not forget the contribution of the microbiota in any single aspect of biology.     

16S rRNA sequencing analysis: the devil is in the details

ABSTRACT

User-friendly computational tools for 16S ribosomal RNA (rRNA) sequencing analysis enable researchers who are not bioinformaticians to analyze and interpret sequencing data from microbial communities. These tools’ easy-to-use interfaces belie the sophisticated and rapidly-evolving science of their underlying algorithms. When analyzing 16S data from a simple microbiome experiment, we found that superficially unimportant decisions about the bioinformatic pipeline led to results with radically different biological interpretations. We share these results as a cautionary tale whose moral is that, in 16S analysis, the devil is in the details. Wet bench researchers should therefore strongly consider partnering with bioinformaticians or computational biologists when analyzing 16S data.     

Commensal-pathogen interactions in the intestinal tract

The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other’s persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode parasite, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations.