Newborn Gastrointestinal Tract Research Articles

From vacant to vivid: The nutritional landscape drives infant gut microbiota establishment.

From the moment of birth, the newborn gastrointestinal tract is infiltrated by various bacteria originating from both maternal and environmental sources. These colonizing bacteria form a complex microbiota community that undergoes continuous changes until adulthood and plays an important role in infant health. The maturation of the infant gut microbiota is driven by many factors and follows a distinct patterned trajectory, with specific bacterial taxa establish in the intestine in accordance with developmental milestones as the infant grows. In this review, we highlight how elements such as diet and host physiology select for specific microbial functions and shape the composition of the bacterial community in the large intestine.

Exploring the prevalence of birth defects of the gastrointestinal tract in newborns: A Six-year analysis in Bogotá, Colombia

BackgroundBirth defects (BD) occur in 3–6 % of live births (LB) and constitute significant morbimortality and disability. Some BD of the gastrointestinal (GI) tract requires surgical interventions during the first days of life. Knowing the prevalence in different city areas could guide decision-makers in developing public policies that guarantee timely attention. This study aims to determine the prevalence of 7 GI defects in LB in Bogotá, Colombia, and to explore factors related to their occurrence. MethodsWe conducted an analytical cross-sectional observational study based on data from the BD database of the Public Health Surveillance System (PHSS) of Bogotá between 2015 and 2021, using all available records where BD of the GI tract was reported. We performed descriptive analyses in Jamovi and correlation analyses in SPSS. ResultsWe included 869 cases in the study. GI defects occurred more frequently in males (50.5 %). Esophageal atresia was the BD most frequently reported (25.9 %), followed by gastroschisis and anorectal malformation (19 %). GI defects are more frequent in the city's center-east area of Bogota. The prevalence of GI defects in Bogota during the period studied was 14.2 per 10,000 LB. Of the LB with GI defects, 93.8 % had low socioeconomic status. ConclusionsThe results of this study point to the importance of centralizing neonatal surgical care services for these pathologies in the sub-network that serves this population. Prenatal care, housing conditions, and substance use in the home were related to a higher prevalence of GI defects.

Analysis of the gut microbiota using MALDI-TOF and cultural techniques in breastfed infants delivered vaginally and through caesarean section

Objectives: The gastrointestinal tract of newborns is colonised immediately after birth with microbes from the environment, mainly from the mother. According to studies, the early neonatal microbiota is crucial for developing the postnatal immune system. The objective of this study was to investigate the relationship between neonatal gut flora and the mode of delivery during gut microbiota colonisation. Material and Methods: A total of 30 neonates – 16 born vaginally and 14 by caesarean section – participated in this study of the intestinal bacterial composition at 3 days of age. Stool cultures and matrix-assisted laser desorption ionisation time-of-flight analyses determine aerobic and anaerobic bacterial species. Results: Neonates delivered by caesarean section appeared to have a less diverse gut microbiota regarding bacterial species than vaginally delivered neonates. Bifidobacterium species are absent from the gut microbiota after caesarean delivery. Even though every newborn vaginally born had a unique microbial profile, the most prevalent bacterial species were Streptococcus spp., Veillonella atypica, Bacteroides vulgatus and Bifidobacterium spp. Conclusion: Our results suggest that the mode of birth significantly influences the gut microbiota composition in the 1st year of human life. This study opens the path to further investigations to confirm the link between microbiota composition and enterotypes of the gut microbiome of breastfed neonates. In addition, we underline the importance of MALDI-TOF for species-level identification of organisms within a fraction of a second.

Development of the Gastrointestinal Tract in Newborns as a Challenge for an Appropriate Nutrition: A Narrative Review.

The second and third trimesters of pregnancy are crucial for the anatomical and functional development of the gastrointestinal (GI) tract. If premature birth occurs, the immaturity of the digestive and absorptive processes and of GI motility represent a critical challenge to meet adequate nutritional needs, leading to poor extrauterine growth and to other critical complications. Knowledge of the main developmental stages of the processes involved in the digestion and absorption of proteins, carbohydrates, and lipids, as well as of the maturational phases underlying the development of GI motility, may aid clinicians to optimize the nutritional management of preterm infants. The immaturity of these GI systems and functions may negatively influence the patterns of gut colonization, predisposing to an abnormal microbiome. This, in turn, further contributes to alter the functional, immune, and neural development of the GI tract and, especially in preterm infants, has been associated with an increased risk of severe GI complications, such as necrotizing enterocolitis. Deeper understanding of the physiological colonization patterns in term and preterm infants may support the promotion of these patterns and the avoidance of microbial perturbations associated with the development of several diseases throughout life. This review aims to provide a global overview on the maturational features of the main GI functions and on their implications following preterm birth. We will particularly focus on the developmental differences in intestinal digestion and absorption functionality, motility, gut–brain axis interaction, and microbiomes.

Современные подходы к профилактике некротизирующего энтероколита у недоношенных новорожденных

Necrotizing enterocolitis (NEC) is the most life-threatening disease of the gastrointestinal tract in newborns. Current strategies and methods of NEC prevention affect the pathogenetic mechanisms of the disease development. The promotion of breastfeeding and the use of early minimal enteral nutrition with native breast milk are the main links in prevention. Immunoglobulins, antiinflammatory cytokines, and other biologically active substances found in breast milk prevent the development of NEC. A change in diet and the use of donor milk lead to a decrease in the incidence of NEC. The use of antenatal steroids in women at risk of preterm birth, control of hypoxia and normalization of the respiratory parameters also reduce the risk of NEC development. For normal colonization of the intestine, the use of probiotics is recommended. The use of oral antibacterial drugs, which are recommended in some multicomponent methods of prevention, often leads to negative results. The use of oral antifungal drugs in modern neonatology is not excluded. The use of oral immunoglobulins is ineffective. Key words: necrotizing enterocolitis, breast milk, enteral antibiotics, oral antifungal drugs, probiotics

Pathomorphological and etiological characteristics of infectious liver injury and gastrointestinal tract in newborns

Aim study . To study the etiology, nosological structure and pathomorphological changes in the liver and gastrointestinal tract in deceased newborns with perinatal infectious diseases. Materials and methods . In total, 48 protocols of pathological autopsy of the deceased newborns were studied in 2018 and 2019. Gender, age of newborns, maternal gestational age, post-mortem bacteriological studies, as well as macroand microscopic changes in the gastrointestinal tract and liver were evaluated. Results . Hepatitis and enterocolitis were part of generalized intrauterine infection and early neonatal sepsis — 19 cases each (39.6%), mainly in preterm infants (93.8%). Positive results of bacteriological studies of autopsy material were noted in 12% of cases. The most common causative agent in post-mortem bacteriological examination in early and late neonatal sepsis was Klebsiella pneumoniae . The main morphological manifestations of hepatitis in newborns were lobular hepatitis of various degrees of activity — 63.8%, as well as fetal giant cell hepatitis — 21.4%. Morphological changes in gastroenterocolitis were characterized mainly by the development of erosive-ulcerative enterocolitis (37.8%), productive enterocolitis (46.9%), less often serous-catarrhal, ulcerative-necrotic enterocolitis (6.25%).

Group B streptococcal transmission rates as determined by PCR.

Background Group B Streptococcus (GBS) is a common cause of neonatal sepsis. GBS colonization of the newborn gastrointestinal tract (GIT) may be a critical precursor for late-onset infection. Assessment of the rate of neonatal GBS intestinal colonization has generally relied upon culture-based methods. We used polymerase chain reaction (PCR) and culture to determine the rate of GBS transmission to neonates. We hypothesized that PCR may enhance the detection of neonatal GBS colonization of the GIT, and that the rate will be higher when evaluated with PCR as compared to culture. Methods This was a cross-sectional study, in which mothers who were positive for GBS on routine screening and their healthy infants were eligible for recruitment. Newborn stool was collected after 24 h of life and before hospital discharge, and stored at -80°C for culture and PCR targeting the GBS-specific surface immunogenic protein (sip) gene. Results A total of 94 mother-infant pairs were enrolled; of these pairs, stool was collected from 83 infants. Based on PCR, the overall GBS transmission rate was 3.6% (3/83). The transmission rate was 2.4% (1/41) among vaginal deliveries and 4.8% (2/42) among cesarean deliveries. The results of culture-based transmission detection were identical. Conclusion These results indicate that the rate of GBS transmission is low and that detection may not be enhanced by PCR methods.

Роль пробиотиков в формировании микробиоты кишечника у детей

Intestinal microbiota (IM) plays a key role in colonic fermentation of oligosaccharides, in immunity modulation and in protection against conventionally pathogenic microorganisms. Colonization of gastrointestinal tract in newborns starts with participation of the mother’s vaginal flora and continuous due to breast feeding by means of breast milk oligosaccharides. Both bifidobacteria and lactobacilli are the most common representatives of IM with a number of physiologic effects. The new combined probiotic contains B. breve BR-03 and L. rhamnosus GG strains. Indications and other clinical aspects are discussed.

Gastrointestinal Emergencies in Neonates: What We Should Know

신생아 위장관 응급 질환은 소화관을 따라 어디에서나 발생하는 다양한 장애를 포함한다. 이러한 질환들의 경우 대부분 후천성 질환이 아닌 선천성 기형에 의한 것이나 산전 검사에서 확인되지 않은 경우도 많아 이에 대한 산후 평가가 필요하게 된다. 이 시기의 신생아의 경우 성인과 달리 전산화단층촬영(computed tomography; 이하 CT)과 자기공명영상(magnetic resonance imaging; 이하 MRI)이 제한적인 경우가 많아 초기 복부 방사선 촬영에서의 진단이 중요하게 되어 복부 방사선 촬영에서 보일 수 있는 소견들에 대해 숙지하는 것이 필요하다. 또한 추가적으로 진단에 사용될 수 있는 복부 초음파, 투시 검사의 소견, 적응증에 대해 이해하는 것이 진단과 이에 따른 적절한 처치를 위해 중요하다. 이에 이 논문에서는 신생아 위장관 응급 질환에서 나타날 수 있는 다양한 영상 소견에 대해 기술하고 정리하였다.

Intestinal mucosal lymphocytes in neonatal sepsis

We studied the autopsy material obtained from 7 children who died in the neonatal period in order to evaluate the composition of lymphocytes of the intestinal mucosa against the background of morphological changes in the tissues of the gastrointestinal tract in newborns with sepsis. The main group consisted of 4 children with neonatal sepsis, the control group – of 3 newborns who died from other causes. The research material included the specimen of the small and large intestine.Results. Small intestine: it was found that there were less CD4 + lymphocytes in the small intestinal mucosa in the group of children who died from neonatal sepsis in 75% of cases than in the control group, but this difference was not statistically significant (p=0.1). There were no differences in the number of CD8 + and CD20 + cells in the studied groups. Large intestine: the number of CD4 + lymphocytes of the mucous membrane of the colon was greater in the main group of children than in the control group (p=0.03). An increase in the number of CD4 + cells was registered in 3 of 4 cases of neonatal sepsis. The number of CD8+ and CD20+ lymphocytes in the studied groups was the same (р>0.05).Conclusion. The increase in T-lymphocytes CD4+ in the mucous membrane of the large intestine is probably connected with the antigenic stimulation of opportunistic intestinal bacteria. We found no morphological signs of the suppression of the cells of adaptive immunity associated with the intestinal mucosa.

A Novel Animal Model for Regional Microbial Dysbiosis of the Pioneer Microbial Community.

Pioneer microbiota colonizing the newborn gastrointestinal tract has long-lasting effects on host health. Restoration of the gut microbial community, following dysbiosis during the neonatal period, may be one strategy to prevent undesirable health outcomes linked to an altered neonatal gut microbiome. Without appropriate animal models that recreate the prolonged human neonatal developmental period it is not possible to effectively analyze interventions designed to restore regional microbial populations. Our study used a lamb model in which intestinal segments were surgically isolated (blind-ended) in fetal lambs to create early microbial dysbiosis by delaying post-natal exposure to intestinal ingesta. Intestinal segments isolated in utero retained blood flow, innervation, and lymphatic drainage through the mesenteric attachment. Continuity of the fetal gastro-intestinal tract was re-established by side-to-side anastomosis of intestine proximal and distal to each isolated intestinal segment. Microbial restoration was then implemented in neonatal lambs by reconnecting a portion of the in utero isolated intestinal segments to adjacent intestinal tract 1 and 7 days after birth. Bacterial communities colonizing the adjacent intestine, in utero isolated intestinal segments, and reconnected intestinal segments were profiled using 16S amplicon sequencing on days 1, 7, and 56 of age. The in utero isolated intestinal segments were colonized 1 day after birth but the density of active bacteria was reduced and community composition altered when compared to adjacent intestine. Proteobacteria dominated the adjacent small intestine at early time points (day 1 and day 7) with a shift to primarily Firmicutes on day 56, consistent with establishment of an anaerobic bacterial community. In contrast, Proteobacteria persisted as the predominant community for 56 days in the in utero isolated intestinal segments. There was, however, almost full restoration of the microbial community composition in the in utero isolated intestinal segments following reconnection to the adjacent intestine. The density of beneficial bacteria, especially Bifidobacterium, remained significantly lower in the reconnected intestinal segments at 56 days when compared to adjacent intestine. Post-natal persistence of a stable pioneer community (Proteobacteria) in the in utero isolated intestinal segments provides a model system to study the temporal effects of regional microbial dysbiosis throughout a prolonged neonatal period.

A Bifidobacterial pilus-associated protein promotes colonic epithelial proliferation.

Development of the human gut microbiota commences at birth, with certain bifidobacterial species representing dominant and early colonisers of the newborn gastrointestinal tract. The molecular basis of Bifidobacterium colonisation, persistence and presumed communication with the host has remained obscure. We previously identified tight adherence (Tad) pili from Bifidobacterium breve UCC2003 as an essential colonisation factor. Here, we demonstrate that bifidobacterial Tad pili also promote in vivo colonic epithelial proliferation. A significant increase in cell proliferation was detectable 5 days postadministration of B. breve UCC2003. Using advanced functional genomic approaches, bacterial strains either (a) producing the Tad2003 pili or (b) lacking the TadE or TadF pseudopilins were created. Analysis of the ability of these mutant strains to promote epithelial cell proliferation in vivo demonstrated that the pilin subunit, TadE, is the bifidobacterial molecule responsible for this proliferation response. These findings were confirmed in vitro using purified TadE protein. Our data imply that bifidobacterial Tad pili may contribute to the maturation of the naïve gut in early life through the production of a specific scaffold of extracellular protein structures, which stimulate growth of the neonatal mucosa.

BCFA-enriched vernix-monoacylglycerol reduces LPS-induced inflammatory markers in human enterocytes in vitro.

BackgroundExcess vernix caseosa produced by the fetal skin appears as particles suspended in the amniotic fluid in late gestation, is swallowed by the fetus, and is found throughout the newborn gastrointestinal tract as the first organisms are arriving to colonize the gut. Lipid-rich vernix contains an unusually high 29% branched chain fatty acids (BCFA). BCFAs reduce the incidence of necrotizing enterocolitis in an animal model, and were recently found predominantly in the sn-2 position of human milk triacylglycerols. Nothing is known about the influence of vernix BCFA on proinflammatory markers in human enterocytes.MethodsWe investigated the effect of vernix-monoacylglycerides (MAGs) (enriched with 30% BCFA) on interleukin (IL)-8 and NF-κB production in a human intestinal epithelial cell line (Caco-2). Caco-2 cells were pretreated with vernix-MAG or vernix-free fatty acid (FFA) prior to lipopolysaccharide (LPS) activation.ResultsBoth vernix-MAG and vernix-FFA increased cell BCFA and eliminated an LPS-induced 20% reduction in cell viability. In stimulated Caco-2 cells, vernix-MAG was more effective than vernix-FFA in suppressing IL-8 and NF-κB. Activated vernix-MAG-treated cells expressed less of the cell-surface Toll-like receptor4 (TLR-4) compared with controls.ConclusionThis is the first study to show the reduction of proinflammatory markers in human cells mediated by BCFA-MAG.

A Novel Mutation in TMPRSS15 Gene Causes a Severe Form of Congenital Enterokinase Deficiency

: Congenital enterokinase deficiency is a rare autosomal recessive disorder of gastrointestinal tract in newborns. Enterokinase initiates digestion of protein by conversion of trypsinogen into trypsin. We analyzed the parents of unaffected deceased newborn with congenital enterokinase deficiency by exome sequencing. The results of exome sequencing identified a novel heterozygous frameshift deletion, c.151-155del p.Ala51Trpfs*5, in TMPRSS15 gene. Direct sequencing confirmed that the couple had heterozygous status. TMPRSS15 gene mutations are completely rare. To date, one small deletion and three nonsense mutations are reported in this gene in Human Gene Mutation Database (HGMD®). The identified mutation leads to complete absence of enzymatic activity.

Differentiated approach to intestinal stoma formation in infants with necrotizing enterocolitis and gastrointestinal tract malformation, intestinal stoma complications.

Modern methods of early prenatal and postnatal diagnosis of malformations and acquired acute inflammatory diseases of the gastrointestinal tract of newborns make it possible to perform timely early surgical correction. However, to date, remain relevant and controversial issues of palliative surgical interventions in landmark surgical correction bowel disease. This is due to the fact that the implementation of radical correction of newborns with congenital or acquired intestinal development of acute surgical diseases of the intestine without the formation of a stoma increases the risk of undesirable serious complications. Therefore, a significant group of patients in need of staged surgical treatment with the initial formation of an intestinal stoma. To date, there is also no unified management of patients with surgical stage of neonatal necrotizing enterocolitis. Among the options of surgical care to patients with perforated NEC have supporters’ resection with primary anastomosis and supporters with the phased withdrawal of treatment with intestinal stoma followed by reconstructive surgery. Even at the present stage of development of surgical care to the formation of intestinal stomas may be accompanied by tactical, technical errors, and improper care of ostomy leads to the development of local or systemic complications, significantly impair a patient's quality of life, lead to an increase in time and cost of treatment of the underlying disease. Currently there is no common standard and indications for the overlay of intestinal stoma, the level of its formation, the duration of existence, and the existing number of possible causes complications to choose an individual approach in the treatment of this patient group.

Modern possibilities of diagnostic and surgical treatment of neonatal necrotizing enterocolitis. (Review article)

In recent years there has been an increase in the number of infants with low birth weight and preterm infants undergoing antenatal and intrapartum hypoxia, which leads to an increase in the number of severe diseases of the gastrointestinal tract, such as necrotizing enterocolitis (NEC) of newborns. NEC is known to be one of the most common acquired diseases of the gastrointestinal tract of newborns in neonatal departments and intensive care units, which in some cases require urgent surgical intervention. From a clinical point of view, NEC occurs as mild and severe complications in the form of necrosis of the intestinal wall, peritonitis, sepsis causing high mortality. As to understanding of NEC pathophysiology, it is considered to be of a multifactorial nature of damage with the development of excessive intestinal wall inflammation of a relative immaturity of the intestine in response to intestinal ischemia. The final result is a cascade of immune system activation and release of proinflammatory cytokines, which leads to spread determined inflammatory response. In the world practice, Walsh M., Kleigman R. classification (1986) is the most common, taking into account stage changes of clinical, radiographic, and gastrointestinal symptoms. However, the diagnosis is complicated by NEC nonspecific clinical picture and the lack of accuracy of additional methods of examination, the absence of specific markers. Diagnostic criteria are based on NEC clinical, laboratory and instrumental methods of research. Many serological markers for the diagnosis of necrotizing enterocolitis are suggested, including: C-reactive protein, platelet activating factor, binding protein intestinal fatty acid, fecal calprotectin, matrix metalloproteinase inhibitors of matrix metalloproteinases, Claudin-3, endogenous antimicrobial peptide cathelicidin, citrulline, but there is no consensus as to their use in terms of clinical benefit. The most valuable objective diagnostic methods used to examine newborns during the active phase of NEC are plain radiography of the abdomen and ultrasound examination of the abdomen. Application of X-ray contrast examinations of the gastrointestinal tract, computed tomography and magnetic resonance imaging is not considered useful in clinical practice to diagnose NEC. In their studies, the authors have shown great benefit using color Doppler ultrasound to assess the thickness of the intestinal wall, echogenicity, motility and perfusion in healthy infants and children with NEC. Recently, there have been reports concerning the use of non-invasive methods to diagnose cerebral and visceral blood flow using near-infrared spectroscopy. Among invasive methods of NEC diagnosis, which are used in case of serious condition of the patient and a significant increase in abdominal circumference, abdominocentesis is applied. The treatment of therapeutic stages of NEC is standard almost in all hospitals and it includes: enteral pause, parenteral nutrition, infusion, antibiotic therapy, administration of inotropic drugs, blood products, correction of electrolyte and acid - base balance of the blood, dynamic monitoring. The most common method of surgical treatment of perforated NEC is laparotomy, bowel resection, or removal enterostoma, application of primary anastomosis, the use of peritoneal drainage as a preoperative preparation, or as an independent method of surgical treatment. There is currently no convincing prospective controlled studies of the effect of application of specific surgical approach to the results of survival. Among the alternatives to laparotomy the authors propose to use laparoscopy, which can be a useful tool in the arsenal of diagnostics and surgical treatment of NEC, it can be used in infants with suspected NEC, to avoid unnecessary laparotomy when there is no confidence in the need for surgery and to minimize surgical trauma. Surgical treatment for NEC is not standardized. There are no clear indications for surgical treatment, type of the surgery, and technical aspects. Keeping babies with NEC is a common problem of neonatologists, pediatric surgeons and intensive care specialists. Nowadays, there is no uniform standard of care for patients with this disease, and the suggested methods of surgical treatment have confused results. Despite a large number of methods to diagnose NEC, the issues of early pre-clinical diagnosis as well as the extensive use of laboratory-instrumental predictors of NEC, the course and progression of complications of the disease remain unsolved. Despite a large number of proposed methods of surgery surgical treatment of NEC remains complicated, there are certain problems concerning the use of these methods at each surgical stage of NEC. Early diagnosis, unified and at the same time an individual choice of surgical tactics on every step of surgery of NEC will reduce mortality, complications and disability in this group of patients. The objective of this article is to review current capabilities of diagnosis and surgical treatment of infants with NEC.

Core Concepts: Intestinal Perfusion in the Perinatal Period

The transitional physiology during the perinatal period facilitates adaptation from fetal to neonatal life and allows the gastrointestinal tract to assume essential postnatal functions. Intrinsic hemodynamic control in the developing intestines matures as a function of postnatal age. Immature vascular regulation in the newborn gastrointestinal tract is offset by an enhanced ability to extract oxygen from blood, and to some extent by increases in intestinal perfusion. Vasodilatation in the neonatal intestine is near maximal. Therefore, additional stressors particularly during the postprandial period increase the risk of mismatches in the oxygen supply to demand ratio, potentially predisposing intestinal tissue to hypoxia and ischemic injury.

Effect of Routine Lactobacillus reuteri DSM 17938 use on Rates of Late-onset infection in Extremely-low-birth-weight Infants

Background: Preterm infants are at high risk for late-onset infections due to gram-negative or fungal organisms. Evidence supports that a common source for these organisms may be the gastrointestinal tract. One theoretical way to change the infection rate is to alter the bacterial flora inhabiting the newborn gastrointestinal tract using probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of late-onset gram-negative and fungal infection in neonates with birth weight ≤ 1000 grams. Methods: This is a retrospective cohort study comparing the rates of gram-negative bacterial and fungal infections in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri, and neonates born July 2009 through July 2012 who received routine L. reuteri prophylaxis. Neonates were excluded if they died or were transferred within the fi rst week of life. The remainder were included in the study and recorded as either having late onset infection related to gram negative organisms or fungi, or not having late onset infection. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of infection were compared using Chi square analysis with Fisher exact t-test. Results: Medical records for 354 neonates were reviewed, 232 before- and 122 after-introduction of L. reuteri prophylaxis. Despite a marked reduction in necrotizing enterocolitis and mortality, the incidence of late-onset infection varied from year-to-year, but was not signifi cantly altered by the introduction of routine L. reuteri. No adverse events related to use of L. reuteri were noted. Conclusions: Prophylactic initiation of L. reuteri as a probiotic does not decrease late-onset infection.

An increase in milk IgA correlates with both pIgR expression and IgA plasma cell accumulation in the lactating mammary gland of PRM/Alf mice

In mice, during late pregnancy and lactation, maternal precursors of IgA-containing cells (cIgA-cells) are primed in the gut and home to the mammary gland where they secrete IgA. In turn, the ensuing increase in milk IgA mediates immune protection of the newborn gastrointestinal tract. PRM/Alf is an inbred mouse strain which exhibits a substantial post-natal intestinal lengthening which develops throughout the neonatal suckling period, suggesting that the availability of cIg-A cells and the level of protective IgA in milk might also be increased. We confirmed that PRM/Alf milk contains higher amounts of IgA than C57BL/6J throughout lactation, concomitantly with an increase of pIgR on epithelial cells and a higher density of cIgA-cells in the PRM/Alf mammary gland. Furthermore, a search for variations in cellular and humoral factors implicated in regulating cIgA-cell migration towards the mammary gland, including the vascular addressins MAdCAM-1 (mucosal addressin cell adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) as well as the mucosal epithelial chemokine CCL28, did not reveal any quantitative differences in expression between PRM/Alf and C57BL/6J mice strains. Thus our results indicate that these factors are not limiting in the recruitment of cIgA-cells released from the elongated gut of PRM/Alf mice. In the context of intestinal lengthening, these findings strengthen the notion of an entero-mammary gland link, where the neonatal gut is protected by the maternal gut through the immune function of the mammary gland.

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.