Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

OBJECTIVE: Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. DESIGN: Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. SETTING: General community. SAMPLE: Representative sub-sample of 198 healthy term infants from the CHILD Study. METHODS: Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months. MAIN OUTCOME MEASURES: Infant gut microbiota profiles. RESULTS: In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. CONCLUSIONS: Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. TWEETABLE ABSTRACT: Maternal #antibiotics during childbirth alter the infant gut #microbiome.

Infant gut immunity: a preliminary study of IgA associations with breastfeeding.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (ß-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Infant gut microbiota and food sensitization: associations in the first year of life.

BACKGROUND: The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. OBJECTIVE: To explore associations of infant gut microbiota and food sensitization. METHODS: Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population-based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing. RESULTS: Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food-sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23-0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae. CONCLUSIONS AND CLINICAL RELEVANCE: Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.

Associations between bacterial communities of house dust and infant gut.

The human gut is host to a diverse and abundant community of bacteria that influence health and disease susceptibility. This community develops in infancy, and its composition is strongly influenced by environmental factors, notably perinatal anthropogenic exposures such as delivery mode (Cesarean vs. vaginal) and feeding method (breast vs. formula); however, the built environment as a possible source of exposure has not been considered. Here we report on a preliminary investigation of the associations between bacteria in house dust and the nascent fecal microbiota from 20 subjects from the Canadian Healthy Infant Longitudinal Development (CHILD) Study using high-throughput sequence analysis of portions of the 16S rRNA gene. Despite significant differences between the dust and fecal microbiota revealed by Nonmetric Multidimensional Scaling (NMDS) analysis, permutation analysis confirmed that 14 bacterial OTUs representing the classes Actinobacteria (3), Bacilli (3), Clostridia (6) and Gammaproteobacteria (2) co-occurred at a significantly higher frequency in matched dust-stool pairs than in randomly permuted pairs, indicating an association between these dust and stool communities. These associations could indicate a role for the indoor environment in shaping the nascent gut microbiota, but future studies will be needed to confirm that our findings do not solely reflect a reverse pathway. Although pet ownership was strongly associated with the presence of certain genera in the dust for dogs (Agrococcus, Carnobacterium, Exiguobacterium, Herbaspirillum, Leifsonia and Neisseria) and cats (Escherichia), no clear patterns were observed in the NMDS-resolved stool community profiles as a function of pet ownership.

[A case of myelodysplastic syndrome transforming into acute B-cell lymphoid leukemia]. / Tiszta B-sejtes akut lymphoid leukaemiába transzformálódó myelodysplasticus szindróma esete.

Case history of a seventy year old man with myelodysplastic syndrome is presented. The disease terminated into acute leukaemia in 22 months. The pure, B lymphoid stem cell nature of the leukaemic cells has been proved, beside morphology and cytochemistry, by detailed flow cytometric phenotyping and PCR amplification as well as sequencing of the immunoglobulin heavy chain gene CDR3 region.

[Diagnosis of chronic myeloproliferative diseases based on bone marrow biopsy]. / Krónikus myeloproliferatív betegségek diagnózisa csontvelöbiopsziás minták alapján.

The bone marrow biopsies and laboratory data of 248 patients with untreated chronic myeloproliferative disorders have been evaluated according to the Hannover Classification. 47.6 per cent of the cases were classed as primary or basic diseases, including chronic myeloid leukaemia common type, chronic myeloid leukaemia megakaryocytic type, chronic megakaryocytic-granulocytic myelosis, polycythaemia vera and essential thrombocythaemia. In 52.4 per cent of the biopsies the advanced stages of the primary diseases like increase of fibers and loss of differentiation were noted; the increase of fibers in myeloid leukaemia megakaryocytic type and in chronic megakaryocytic-granulocytic myelosis, and loss of differentiation in chronic myeloid leukaemia common type were frequently noted. In 14.1 per cent of the cases the advanced myelofibrosis and blast cell accumulations obscured the histological features of the primary disease, therefore these cases were placed in the unclassifiable group. The cases without increase of fibers and loss of differentiation accounted for only 4 per cent of the unclassifiable category. Leucocyte and platelet count as well as haematocrit values showed considerable overlapping and scattering and were generally lower in cases which developed myelofibrosis.

Nucleolar organizer regions of megakaryocytes in chronic myeloproliferative disorders.

To study megakaryocyte activation, the argyrophilic staining method of nucleolar organizer regions (AgNOR) has been applied to decalcified bone marrow biopsies of 16 individuals with no haematopoietic disorders and 59 patients with chronic myeloproliferative disease. Of the 59 patients, 18 had chronic myeloid leukaemia (CML), 21 chronic megakaryocytic granulocytic myelosis (CMGM), 13 polycythaemia vera (PV) and 7 essential thrombocythaemia (ET). The AgNOR number of megakaryocytes in CML was significantly lower, and in CMGM, PV and ET significantly higher than in healthy individuals. The high number and the clusters of fine-grained AgNORs of megakaryocytes in CMGM, PV and ET are suggestive of active, proliferating cells. The AgNOR number of megakaryocytes and the platelet counts of the patients did not show a convincing correlation. In CMGM, PV and ET the pyknotic, heterochromatinized megakaryocytes with narrow rims of cytoplasm called bare (nude) nuclei, possessed few, large AgNOR granules. The AgNOR staining of bare nuclei and the roughly identical number of granules found in CMGM, PV and ET indicate a common, active mechanism of apoptosis.

Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia.

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.