The establishment of the gut microbiota in 1-year-aged infants: from birth to family food

none12noAbstract Purpose With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named “A.MA.MI.” (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Methods Forty-five fecal samples were collected at 12 months of infants’ age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. Results At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith’s PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. Conclusion The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life.openMirco Vacca; Benedetta Raspini; Francesco Maria Calabrese; Debora Porri; Rachele De Giuseppe; Marcello Chieppa; Marina Liso; Rosa Maria Cerbo; Elisa Civardi; Francesca Garofoli; Hellas Cena; Maria De AngelisVacca, Mirco; Raspini, Benedetta; Maria Calabrese, Francesco; Porri, Debora; De Giuseppe, Rachele; Chieppa, Marcello; Liso, Marina; Maria Cerbo, Rosa; Civardi, Elisa; Garofoli, Francesca; Cena, Hellas; De Angelis, Mari

Early life microbiota colonization. The A.MA.MI Study

ABSTRACT Background. The intestinal microbiome is relatively dynamic during the first years of life, becoming relatively stable throughout a lifetime, thus dictating adult life's future health. There are many factors influencing gut microbiome composition, including maternal pre-pregnancy, body mass index (BMI), gestational weight gain (WG), type of feeding, weaning timing, and birth/family environment. Objectives. The study aims to investigate the intestinal microbiome development of infants (ages 0-12 months) and to analyze how prenatal and postnatal factors, including maternal BMI and weight gain during pregnancy, type of feeding, time and type of weaning, and the presence of siblings in the family, could influence the infant gut microbiome composition at one year of age. Methods. 63 dyads were enrolled at Neonatal Unit, IRCCS Policlinico San Matteo, Pavia. Anthropometric parameters were assessed before discharge (T0), at 30 days from birth (T1), at 6 months (T2) and 1 year (T3); validated questionnaires were used to evaluate mother’s dietary habits and physical activity at each time. Mothers were interviewed about family environment and infants feeding/supplementation at each time. For each child a stool sample was collected at each time and analyzed using metagenomics 16s ribosomal RNA gene sequence-based methods. Cluster and correlation analysis were used to assess changes in the microbial composition across different follow-up times. Results. At one years of age, pre- and perinatal variables were not significantly associated with any bacterial taxon, while postnatal variables showed the major contribution in shaping microbiota. Feeding and weaning were the main influencing factors. Conclusion. Our findings highlighted that microbial colonization during the first year of life is likely affected by various factors resembling a simultaneous effect of multiple variables. Mainly, different variables play a significant role at different time. Thus, these data contribute to add evidence concerning the complex multifactorial interaction of GI-microbiota depending on the various stimuli during the early stages of life. This study will provide the starting point for a future prospective and observational study assessing the potential association between maternal diet and life-style with newborns microbiome composition, their influence on childhood obesity development and the associated increased risk of NCDs in adulthood.ABSTRACT Background. The intestinal microbiome is relatively dynamic during the first years of life, becoming relatively stable throughout a lifetime, thus dictating adult life's future health. There are many factors influencing gut microbiome composition, including maternal pre-pregnancy, body mass index (BMI), gestational weight gain (WG), type of feeding, weaning timing, and birth/family environment. Objectives. The study aims to investigate the intestinal microbiome development of infants (ages 0-12 months) and to analyze how prenatal and postnatal factors, including maternal BMI and weight gain during pregnancy, type of feeding, time and type of weaning, and the presence of siblings in the family, could influence the infant gut microbiome composition at one year of age. Methods. 63 dyads were enrolled at Neonatal Unit, IRCCS Policlinico San Matteo, Pavia. Anthropometric parameters were assessed before discharge (T0), at 30 days from birth (T1), at 6 months (T2) and 1 year (T3); validated questionnaires were used to evaluate mother’s dietary habits and physical activity at each time. Mothers were interviewed about family environment and infants feeding/supplementation at each time. For each child a stool sample was collected at each time and analyzed using metagenomics 16s ribosomal RNA gene sequence-based methods. Cluster and correlation analysis were used to assess changes in the microbial composition across different follow-up times. Results. At one years of age, pre- and perinatal variables were not significantly associated with any bacterial taxon, while postnatal variables showed the major contribution in shaping microbiota. Feeding and weaning were the main influencing factors. Conclusion. Our findings highlighted that microbial colonization during the first year of life is likely affected by various factors resembling a simultaneous effect of multiple variables. Mainly, different variables play a significant role at different time. Thus, these data contribute to add evidence concerning the complex multifactorial interaction of GI-microbiota depending on the various stimuli during the early stages of life. This study will provide the starting point for a future prospective and observational study assessing the potential association between maternal diet and life-style with newborns microbiome composition, their influence on childhood obesity development and the associated increased risk of NCDs in adulthood

Studio dei geni Cyclin-Dependent Kinase Inhibitor CDKN1B/p27 e CDKN2A/p16 e del gene Aryl Hydrocarbon Receptor-Interacting Protein (AIP) negli adenomi paratiroidei sporadici

In questa tesi è stato valuto il possibile interessamento di nuovi geni nela patogenesi molecolare degli adenomi paratiroidei sporadici. I tre geni studiati, CDKN1B/p27, CDKN2A/p16 ( della famiglia degli inibitri delle ciclina-chinasi-dipendenti)e il gene oncosoppressore Aryl Hydrocarbon Receptor Interacting Protein sono stati studiati attraverso l'analisi di sequenza del DNA codificante

Dietary Patterns and Weight Status in Italian Preschoolers with Autism Spectrum Disorder and Typically Developing Children

Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life

Prenatal and postnatal determinants in shaping offspring's microbiome in the first 1000 days: study protocol and preliminary results at one month of life

BACKGROUND:Fetal programming during in utero life defines the set point of physiological and metabolic responses that lead into adulthood; events happening in "the first 1,000 days" (from conception to 2-years of age), play a role in the development of non-communicable diseases (NCDs). The infant gut microbiome is a highly dynamic organ, which is sensitive to maternal and environmental factors and is one of the elements driving intergenerational NCDs' transmission. The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the correlation between several factors, from conception to the first year of life, and infant gut microbiome composition. We described the study design of the A.MA.MI study and presented some preliminary results. METHODS:A.MA.MI is a longitudinal, prospective, observational study conducted on a group of mother-infant pairs (n = 60) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected at T0, T1, T2 and T3, respectively before discharge, 1,6 and 12 months after birth. Maternal and infant anthropometric measurements were assessed at each time. Other variables evaluated were: pre-pregnancy/gestational weight status (T0), maternal dietary habits/physical activity (T1-T3); infant medical history, type of feeding, antibiotics/probiotics/supplements use, environment exposures (e.g cigarette smoking, pets, environmental temperature) (T1-T3). Infant stool samples were planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods. RESULTS:Birth mode (cesarean section vs. vaginal delivery) and maternal pre pregnancy BMI (BMI < 25 Kg/m2 vs. BMI ≥ 25 Kg/m2), significant differences were found at genera and species levels (T0). Concerning type of feeding (breastfed vs. formula-fed), gut microbiota composition differed significantly at genus and species level (T1). CONCLUSION:These preliminary and explorative results confirmed that pre-pregnancy, mode of delivery and infant factors likely impact infant microbiota composition at different levels. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04122612

Early Life Microbiota Colonization at Six Months of Age: A Transitional Time Point

Background: Early life gut microbiota is involved in several biological processes, particularly metabolism, immunity, and cognitive neurodevelopment. Perturbation in the infant’s gut microbiota increases the risk for diseases in early and later life, highlighting the importance of understanding the connections between perinatal factors with early life microbial composition. The present research paper is aimed at exploring the prenatal and postnatal factors influencing the infant gut microbiota composition at six months of age. Methods: Gut microbiota of infants enrolled in the longitudinal, prospective, observational study “A.MA.MI” (Alimentazione MAmma e bambino nei primi MIlle giorni) was analyzed. We collected and analyzed 61 fecal samples at baseline (meconium, T0); at six months of age (T2), we collected and analyzed 53 fecal samples. Samples were grouped based on maternal and gestational weight factors, type of delivery, type of feeding, time of weaning, and presence/absence of older siblings. Alpha and beta diversities were evaluated to describe microbiota composition. Multivariate analyses were performed to understand the impact of the aforementioned factors on the infant’s microbiota composition at six months of age. Results: Different clustering hypotheses have been tested to evaluate the impact of known metadata factors on the infant microbiota. Neither maternal body mass index nor gestational weight gain was able to determine significant differences in infant microbiota composition six months of age. Concerning the type of feeding, we observed a low alpha diversity in exclusive breastfed infants; conversely, non-exclusively breastfed infants reported an overgrowth of Ruminococcaceae and Flavonifractor. Furthermore, we did not find any statistically significant difference resulting from an early introduction of solid foods (before 4 months of age). Lastly, our sample showed a higher abundance of clostridial patterns in firstborn babies when compared to infants with older siblings in the family. Conclusion: Our findings showed that, at this stage of life, there is not a single factor able to affect in a distinct way the infants’ gut microbiota development. Rather, there seems to be a complex multifactorial interaction between maternal and neonatal factors determining a unique microbial niche in the gastrointestinal tract