婴儿肠道双歧杆菌多样性的研究进展

双歧杆菌是婴儿肠道中最丰富的微生物,对婴儿肠道微生物的成熟和稳定有显著影响,与婴儿健康紧密相关。大量研究表明,婴儿肠道中最广泛存在的双歧杆菌有长双歧杆菌、短双歧杆菌和两歧双歧杆菌。母婴之间垂直传递可直接影响婴儿肠道中双歧杆菌各种属的早期定植和相对丰度变化,特别是分娩方式和喂养方式会显著影响婴儿肠道双歧杆菌。此外,胎龄和辅食等因素对婴儿肠道中双歧杆菌的组成与多样性也有一定影响。本文对婴儿肠道双歧杆菌的种属组成、相对丰度变化以及影响其多样性的因素进行了综述,为婴儿双歧杆菌群落的认识提供一定的理论依据。     

孕妇肠道菌群与婴幼儿肠道菌群及肥胖的关系研究进展

女性妊娠过程中,身体的生殖、消化、内分泌等系统会发生一系列变化,孕妇的肠道菌群也会发生相应变化。母亲肠道菌群与子代肠道菌群密切相关,婴幼儿生命早期肠道菌群的来源主要有母亲肠道菌群、母亲阴道菌群和母亲体表菌群,出生以后婴幼儿肠道菌群的定殖主要受喂养方式、生活环境、抗生素暴露等因素的影响。此外,人体肠道菌群功能强大,其可通过调节人体营养物质吸收和外周器官的代谢而成为影响肥胖的一种重要的内环境因素。综述孕妇妊娠期间包括孕早期、孕中期、孕晚期肠道菌群的变化和影响婴幼儿肠道菌群定殖的主要因素,以及对子代肥胖的影响,以期为临床医务人员对预防和控制婴幼儿肥胖提供参考。     

肠道菌群对新生儿神经发育的影响

新生儿肠道菌群的定植和建立是一个复杂的动态演变过程,且易受分娩方式、喂养方式、胎龄、抗生素暴露等多种因素的影响。肠道菌群不仅在新生儿生理发育、免疫系统成熟、抵抗病原体入侵、维护肠道屏障等方面发挥重要作用,还影响神经回路的建立、髓鞘的形成和血脑屏障的形成。早期肠道菌群失调可导致新生儿坏死性小肠结肠炎、生长发育迟缓和智力发育落后等。近年来肠道菌群通过肠-脑轴影响新生儿神经发育受到广泛关注,其主要与代谢、免疫、迷走神经和神经内分泌等途径相关。本文主要就新生儿肠道菌群特征及其影响因素和肠道菌群对神经发育的影响作一综述。     

肠道菌群与免疫的相关性研究

由大量微生物构成的复杂微生物群落栖息在人体的肠道内,这些微生物统称作肠道菌群。肠道菌群在人体的消化吸收、免疫、生物拮抗、抗肿瘤等各项生命活动中发挥着重要的作用。近年来的许多研究提示,肠道内复杂的微生物群落和人体的免疫系统间存在着极为密切的关系。免疫系统发挥正常的功能及建立免疫的稳态与肠道菌群的作用密不可分。研究表明肠道菌群能阻止致病微生物入侵从而影响肠道免疫系统,同时还能影响全身免疫系统,在人体的自身免疫性疾病中有较为重要的作用。     

小于胎龄儿肠道菌群的前瞻性研究CSCD

目的调查小于胎龄(small for gestational age,SGA)儿出生早期肠道菌群特征,探究肠道菌群丰度对婴儿发育的影响。方法选择2021年7月至2022年2月在杭州市临平区妇幼保健院产科孕检母亲40例、出生婴幼儿40例作为研究对象,将分娩SGA婴儿妊娠妇女与分娩适于胎龄(appropriate for gestational age,AGA)婴儿妊娠妇女1∶1进行配对,匹配指标包括是否足月、BMI值是否在正常范围、母亲年龄±5岁以及顺产,作病例对照研究。符合入组标准的产妇40例,其中分娩SGA婴儿母亲20例,为SGA_M组;分娩AGA婴儿母亲20例,为Control_M组。对应新生儿40例,其中SGA婴儿20例,为SGA_C组;AGA婴儿20例,为Control_C组。采用高通量16S rRNA基因测序技术明确SGA婴儿肠道菌群的定植情况,采用Illumina NovaSeq 6000测序系统对V3~V4可变区进行高通量测序,获取肠道菌群的丰度和多样性分布情况。结果SGA组婴儿肠道内大肠埃希菌、双歧杆菌、肠球菌及乳杆菌拷贝数量均显著低于对照组(均P<0.05);基于alpha多样性Chao1指数的分析,估计群落中包含物种的数目,可以看出对照组与SGA组之间物种数目差异极显著;基于beta多样性主坐标分析PCoA的Unweighted_uniFrac_PCoA图,对照组和SGA组之间物种丰度有差异,ANOSIM,R=0.5,P<0.01。在科水平中,Lactobacillaceae、Enterobacteriaceae及Bifidobacteriaceae在4个组中差异均有统计学意义(均P<0.05)。在LEfSe分析中,与SGA组比较,对照组中差异显著的优势菌群数量较少,仅g_Leuconnostoc、f_Lactobacillaceae及g_Dongia为显著上调差异菌;而在SGA组中,差异上调菌群为g_Rothia、f_Micrococcaceae及o_Micrococcales,这些菌同样在SGA_M组与Control_M组比较中为SGA_M组显著上调的差异菌。结论SGA婴幼儿肠道菌群的丰富度和多样性个体间变异度高,致病菌占优,易导致患儿出现肠道微生态系统失衡,其与败血症等SGA婴幼儿并发症具有密切相关性。     

女性阴道微生态状况与母婴健康

女性阴道是自然开放的腔道,其内寄居着大量的微生物,其中乳杆菌占优势。正常阴道内的微生物对于维持女性生殖系统健康具有重要作用,而多种因素能够影响妇女正常的阴道微生态环境,包括妊娠。女性阴道微生态状况不仅会影响自身健康,同时能够影响子代的健康。正常的肠道菌群参与机体的营养、免疫、代谢、神经内分泌等多种生理功能,而婴儿期是人肠道菌群建立的关键时期,其中分娩方式对婴儿菌群的定植和发展具有重要的影响。阴道菌群失衡不但可导致妇女感染性疾病的发生,还与妊娠结局及婴儿菌群的建立密切相关,改善女性阴道微生态状况对提高母婴健康具有重要意义。     

肥胖孕妇肠道菌群与子代肥胖的相关性

妊娠期肥胖发生率在世界范围内呈上升趋势,成为影响人类健康的公共卫生问题。肥胖母亲肠道菌群失调导致婴儿早期定植菌群异常,而婴儿早期菌群定植情况与其日后生长发育密切相关,容易导致成年后出现肥胖、胰岛素抵抗、代谢综合征等疾病。因此针对肥胖孕妇肠道菌群分析,以及婴儿肠道菌群及生长发育的分析,对于孕妇孕期管理、健康宣教提高国民整体身体素质具有重要意义。     

食物过敏婴儿和健康儿肠道菌群分析

目的检测食物过敏婴儿与健康婴儿的大便菌群,为食物过敏与肠道菌群关系的研究提供依据。方法以在重庆儿童医院体检的52例食物过敏婴儿和年龄、性别匹配的100例健康婴儿为研究对象,收集所有对象的新鲜粪便,采用直接快速涂片法分析肠道菌群。结果食物过敏婴儿革兰阳性杆菌比例降低,革兰阴性杆菌、革兰阳性球菌比例增高[(71.43±8.70)%vs(78.91±9.25)%,(15.69±6.26)%vs(11.85±6.66)%,(11.67±4.02)%vs(7.60±4.27)%,P均<0.001]。不同喂养方式下,食物过敏婴儿的大便菌群比例显示不同的改变,但革兰阳性杆菌比例降低是其共同的特点(P均<0.05)。结论食物过敏婴儿肠道菌群与健康婴儿的肠道菌群差异存在显著性。不同喂养方式的婴儿显示不同的大便菌群组成。肠道正常菌群的改变可能在食物过敏的发生中起一定作用。     

喂养方式对西安地区0～2个月婴儿肠道菌群的影响

目的 探讨母乳和混合喂养方式对西安地区婴儿肠道菌群的影响。方法 收集24例0～2月龄西安地区健康婴儿粪便样本,根据婴儿的喂养方式,将样本分为母乳喂养组（17例）和以奶粉为主的混合喂养组（7例）。利用16S rRNA基因测序技术对不同喂养方式的婴儿肠道菌群进行测序,比较不同喂养方式对婴儿肠道菌群多样性和菌群差异的影响。结果 母乳喂养组婴儿粪便样本Ace指数和Chao1指数显著高于混合喂养组（t=4.886, P<0.05; t=6.855, P<0.05）, Shannon指数显著低于混合喂养组（t=2.126,P<0.05）。门水平上,2组样本均以放线菌门、厚壁菌门、变形菌门和拟杆菌门为主,但比例存在差异。相比混合喂养组,母乳喂养组婴儿粪便样本放线菌门和拟杆菌门丰度显著升高（U=6,P<0.05;U=0,P<0.05）,厚壁菌门和变形菌门丰度显著降低（U=24,P<0.05;U=16,P<0.05）。属水平上,母乳喂养组婴儿粪便样本双歧杆菌相对丰度（72.04%）显著升高,同时发现罗氏菌属和葡萄球菌属相对丰度也高于混合喂养组（U=17,P<...     

分娩方式对北京地区持续母乳喂养的34周龄婴儿肠道菌群影响

[目的] 比较持续母乳喂养条件下不同分娩方式的34周龄婴儿肠道菌群差异,探讨分娩方式对较大婴儿肠道菌群发育的影响。[方法] 在北京地区招募健康足月分娩母乳喂养婴儿,在34周仍然参与随访的持续母乳喂养婴儿共21例,其中剖宫产婴儿16例、阴道分娩婴儿5例,进行肠道菌群的16S rRNA检测。[结果] 两组共21个粪便样本中,共注释到6个门,分别为：疣微菌门、变形菌门、梭杆菌门、厚壁菌门、放线菌门和拟杆菌门;两组共21个样本中共有57个OTU注释到属水平,其中,26个属水平OTU被注释到厚壁菌门,18个属水平OTU被注释到变形菌门,6个属水平OTU被注释到放线菌门,5个属水平OTU被注释到拟杆菌门,梭杆菌门、疣微菌门各有1个属水平OTU被注释。其中变形菌门在阴道分娩组（44.17%）肠道菌群中的含量高于剖宫产组（16.10%）;而放线菌门在阴道分娩婴儿（0.00%）肠道菌群中的含量低于剖宫产婴儿（0.09%）。阴道分娩组与剖宫产组相比,共有7个菌属的丰度发生了显著降低（P<0.05）,分别为副杆菌属、葡萄球菌属、嗜血杆菌属、乳杆菌属、肠球菌属、双歧杆菌属及一注释到科水平的毛螺旋菌科OTU。[结论] 分娩方式对持续母乳喂养的婴儿肠道菌群结构存在影响,且这种影响在出生后34周仍然存在。     

The impact of perinatal probiotic intervention on gut microbiota: double-blind placebo-controlled trials in Finland and Germany

Specific probiotic combinations during early feeding, via the mother or incorporated in early formula-feeding, mold the intestinal microbiota composition in infants. The objective was to analyze the impact of probiotic administration to mother or infant on gut microbiota composition in 6-month-old Finnish and German infants. In Finland probiotics were given to mothers (n = 79) for 2 months prior to and 2 months after delivery. In Germany probiotics were started in infants (n = 81) at weaning, at the latest at 1 month of age, and continued for 4 months. A breast-fed group of 6-month-old infants (22 from Finland, 8 from Germany) were compared. Gut microbiota were analyzed by FCM-FISH and qPCR methods. In breast-fed infants a trend toward higher counts of bifidobacteria was detected in Finland (p = 0.097) as against Germany, where a more diverse microbiota was reflected in higher Akkermansia (p = 0.003), Clostridium histolyticum (p = 0.035) and Bacteroides-Prevotella (p = 0.027) levels and a higher percentage of Akkermansia (p = 0.004). Finnish LPR + BL999 intervention group (Lactobacillus rhamnosus LPR and Bifidobacterium longum BL999) had higher percentages of fecal Lactobacillus-Enterococcus (9.0% vs. 6.1% placebo, p = 0.003) and lower bifidobacteria levels (10.03 log cells/g vs. 10.68 log cells/g placebo, p = 0.018). Probiotic treatment had different impacts on gut microbiota composition in Finnish and German infants due to differences in mode of feeding and the early commensal microbiota. Probiotic treatment had different impacts on gut microbiota composition in Finnish and German infants due to differences in mode of feeding and the basic commensal microbiota.     

Transmission of intestinal Bifidobacterium longum subsp. longum strains from mother to infant, determined by multilocus sequencing typing and amplified fragment length polymorphism

The gastrointestinal tracts of neonates are colonized by bacteria immediately after birth. It has been discussed that the intestinal microbiota of neonates includes strains transferred from the mothers. Although some studies have indicated possible bacterial transfer from the mother to the newborn, this is the first report confirming the transfer of bifidobacteria at the strain level. Here, we investigated the mother-to-infant transmission of Bifidobacterium longum subsp. longum by genotyping bacterial isolates from the feces of mothers before delivery and of their infants after delivery. Two hundred seven isolates from 8 pairs of mothers and infants were discriminated by multilocus sequencing typing (MLST) and amplified fragment length polymorphism (AFLP) analysis. By both methods, 11 strains of B. longum subsp. longum were found to be monophyletic for the feces of the mother and her infant. This finding confirms that these strains were transferred from the intestine of the mother to that of the infant. These strains were found in the first feces (meconium) of the infant and in the feces at days 3, 7, 30, and 90 after birth, indicating that they stably colonize the infant's intestine immediately after birth. The strains isolated from each family did not belong to clusters derived from any of the other families, suggesting that each mother-infant pair might have unique family-specific strains.     

婴幼儿呼吸道微生物群演替研究进展

婴幼儿从出生开始正常呼吸道微生物就无时不刻地进行着演替,最终呼吸系统微生物形成动态平衡。婴幼儿时期是呼吸道微生物群演替的重要时期,也是免疫发育的关键时期,容易受外界因素的影响,这些影响因素包括分娩方式、喂养方式、抗生素、季节、疫苗接种等。研究表明婴幼儿时期的呼吸道微生物的组成和发育会影响微生物群的稳定性,从而影响呼吸道感染和过敏性疾病的发生。现对婴幼儿呼吸道微生物群演替及其影响因素,如分娩方式、喂养方式、抗生素使用、季节、疫苗接种等进行综述。     

Transcriptional Modulation of Intestinal Innate Defense/Inflammation Genes by Preterm Infant Microbiota in a Humanized Gnotobiotic Mouse Model

Background and Aims

It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestine. Thus this earliest microbiota potentially has the greatest opportunity to fundamentally influence intestinal development and immune function. The aim of this study was to characterize the effect of early microbial colonization on global gene expression in the distal small intestine during postnatal gut development.

Methods

Gnotobiotic mouse models with experimental colonization by early (prior to two weeks of life) intestinal microbiota from preterm human infants were utilized. Microarray analysis was used to assess global gene expression in the intestinal epithelium.

Results and Conclusion

Multiple intestinal genes involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication, and immune function are developmental- and intestinal microbiota- regulated. Using a humanized gnotobiotic mouse model, we demonstrate that certain early preterm infant microbiota from prior to 2 weeks of life specifically induce increased NF-κB activation and a phenotype of increased inflammation whereas other preterm microbiota specifically induce decreased NF-κB activation. These fundamental differences correlate with altered clinical outcomes and suggest the existence of optimal early microbial communities to improve health outcomes.     

Mother-to-Infant Transmission of Intestinal Bifidobacterial Strains Has an Impact on the Early Development of Vaginally Delivered Infant's Microbiota

Objectives

Bifidobacterium species are one of the major components of the infant''s intestine microbiota. Colonization with bifidobacteria in early infancy is suggested to be important for health in later life. However, information remains limited regarding the source of these microbes. Here, we investigated whether specific strains of bifidobacteria in the maternal intestinal flora are transmitted to their infant''s intestine.

Materials and Methods

Fecal samples were collected from healthy 17 mother and infant pairs (Vaginal delivery: 12; Cesarean section delivery: 5). Mother''s feces were collected twice before delivery. Infant''s feces were collected at 0 (meconium), 3, 7, 30, 90 days after birth. Bifidobacteria isolated from feces were genotyped by multilocus sequencing typing, and the transitions of bifidobacteria counts in infant''s feces were analyzed by quantitative real-time PCR.

Results

Stains belonging to Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium catenulatum, Bifidobacterium longum subsp. longum, and Bifidobacterium pseudocatenulatum, were identified to be monophyletic between mother''s and infant''s intestine. Eleven out of 12 vaginal delivered infants carried at least one monophyletic strain. The bifidobacterial counts of the species to which the monophyletic strains belong, increased predominantly in the infant''s intestine within 3 days after birth. Among infants delivered by C-section, monophyletic strains were not observed. Moreover, the bifidobacterial counts were significantly lower than the vaginal delivered infants until 7 days of age.

Conclusions

Among infants born vaginally, several Bifidobacterium strains transmit from the mother and colonize the infant''s intestine shortly after birth. Our data suggest that the mother''s intestine is an important source for the vaginal delivered infant''s intestinal microbiota.     

不同食性野生鸟类肠道微生物研究进展

肠道微生物是庞大而多样的微生物群落,通过促进营养摄取、宿主防御、免疫调节等,在维持机体健康方面起着至关重要的作用。宿主外部或内部环境的任何变化都会影响肠道微生物的组成,鸟类具有复杂的生活史和多样化的食性,飞翔生活使它们的生理活动面临更大的选择性压力,导致肠道微生物菌群的变化更加复杂。近年来,随着基因测序技术的发展以及对鸟类肠道微生物研究的日益重视,导致了鸟类肠道微生物研究呈指数增长。但目前的研究主要以家禽为主,野生鸟类肠道微生物报道则相对较少。野生鸟类肠道微生物结构变化及其维持机制等的研究仍处于起步阶段,有较大的研究空间。从植食性、肉食性、杂食性三种食性的鸟类肠道微生物组成及特点、影响因素等方面对前人的文献进行了全面梳理,以期为野生鸟类肠道微生物研究提供参考。总的来说,植食性鸟类肠道微生物多样性最低,以高丰度的变形菌门（Proteobacteria）、厚壁菌门（Firmicutes）为主;而杂食性鸟类肠道微生物多样性最高。遗传、生活史特征、人类活动、城市化、圈养行为等对鸟类肠道微生物的组成具有显著性的影响。     

Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants

Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset.     

Feeding modes shape the acquisition and structure of the initial gut microbiota in newborn lambs

Early gut microbial colonization is important for postnatal metabolic and immune development. However, little is known about the effects of different feeding modes (suckling versus bottle-feeding) or microbial sources on this process in farm animals. We found that suckled and bottle-fed newborn lambs had their own distinct gut microbiota. Results from 16S rRNA gene sequencing and qPCR showed that, compared with suckling, bottle feeding significantly increased the abundances of Escherichia/Shigella, Butyricicoccus, and Clostridium XlVa, while significantly decreased the abundance of Clostridium XI. The higher levels of Escherichia/Shigella in bottle-fed lambs suggest that artificial feeding may increase the number of potential pathogens and delay the establishment of the anaerobic environment and anaerobic microbes. Feeding modes also affected the direct transmission of bacteria from the mother and the environment to newborns. The SourceTracker analysis estimated that the early gut microbes of suckled lambs were mainly derived from the mother's teats (43%) and ambient air (28%); whereas those of bottle-fed lambs were dominated by bacteria from the mother's vagina (46%), ambient air (31%), and the sheep pen floor (12%). These findings advance our understanding of gut microbiota in early life and may help design techniques to improve gut microbiota and health.     

昆虫肠道防御及微生物稳态维持机制

在长期的进化过程中,昆虫形成了独特的肠道防御系统,主要由物理屏障和免疫系统共同作用来抵御外来微生物的入侵。如大部分后生动物一样,昆虫肠道上皮细胞无时无刻不与微生物接触,其种类从有益的共生菌、随食物进入的微生物到影响宿主生命的病原菌。在这样一种复杂的环境中,为了实现防御肠道病原微生物的同时又能维持共生微生物稳定的目的,宿主肠道上皮细胞必须在免疫应激和免疫耐受之间保持一种稳态平衡。Duox-ROS免疫系统和免疫缺陷(immune deficiency,Imd)信号通路作为肠道免疫反应的基本途径,必然参与调节此过程。本文从昆虫肠道防御组成、肠道免疫信号通路作用分子机制以及肠道免疫系统在肠道微生物群落稳态维持中的作用的最新研究进展进行综述。     

海洋鱼类肠道微生物研究进展及应用前景

肠道微生物在动物体内数量庞大、结构复杂,在宿主生长发育过程中发挥着重要作用.淡水鱼类肠道微生物的研究主要集中于其对鱼类生长代谢、营养吸收及免疫调节等方面的影响,海洋鱼类则研究相对较少,且多集中于肠道微生物多样性及其变动影响因素分析.本文在归纳总结鱼类肠道微生物功能及其研究方法的基础上,着重分析肠道微生物在海洋鱼类生长发...