Development of the infant gut microbiome predicts temperament across the first year of life

Abstract Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

Download Full-text

Infant gut microbiome composition is associated with non-social fear behavior in a pilot study

Nature Communications ◽

10.1038/s41467-021-23281-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Alexander L. Carlson ◽

Kai Xia ◽

M. Andrea Azcarate-Peril ◽

Samuel P. Rosin ◽

Jason P. Fine ◽

...

Keyword(s):

Pilot Study ◽

Gut Microbiome ◽

Brain Structures ◽

Experimental Manipulation ◽

Human Infant ◽

Microbiome Composition ◽

Social Fear ◽

Infant Gut Microbiome ◽

First Year Of Life ◽

Fear Behavior

AbstractExperimental manipulation of gut microbes in animal models alters fear behavior and relevant neurocircuitry. In humans, the first year of life is a key period for brain development, the emergence of fearfulness, and the establishment of the gut microbiome. Variation in the infant gut microbiome has previously been linked to cognitive development, but its relationship with fear behavior and neurocircuitry is unknown. In this pilot study of 34 infants, we find that 1-year gut microbiome composition (Weighted Unifrac; lower abundance of Bacteroides, increased abundance of Veillonella, Dialister, and Clostridiales) is significantly associated with increased fear behavior during a non-social fear paradigm. Infants with increased richness and reduced evenness of the 1-month microbiome also display increased non-social fear. This study indicates associations of the human infant gut microbiome with fear behavior and possible relationships with fear-related brain structures on the basis of a small cohort. As such, it represents an important step in understanding the role of the gut microbiome in the development of human fear behaviors, but requires further validation with a larger number of participants.

Download Full-text

Prenatal and postnatal determinants in shaping offspring's microbiome in the first year of life. Preliminary results.

10.21203/rs.2.15679/v1 ◽

2019 ◽

Author(s):

Benedetta Raspini ◽

Debora Porri ◽

Rachele De Giuseppe ◽

Marcello Chieppa ◽

Marina Liso ◽

...

Keyword(s):

Gut Microbiome ◽

Weight Status ◽

Dietary Habits ◽

Mode Of Delivery ◽

Normal Weight ◽

First Year ◽

Microbiota Composition ◽

Microbiome Composition ◽

Infant Gut Microbiome ◽

First Year Of Life

Abstract 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” 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 factors and environmental insults; it modifies its composition over the host’s lifespan and is one of the elements driving this intergenerational NCDs' transmission. The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the possible correlation between pre-natal and post-natal factors and the infant gut microbiome composition, during the first year of life at different follow-up. We describe the study design of the A.MA.MI Study and present some preliminary results.Methods A.MA.MI is a longitudinal, prospective, observational study that includes a group of mother-infant pairs (n=63) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected before discharge (T0) and at 1,6,12 months after birth (T1,T2,T3). Maternal and infant anthropometric measurements are assessed at each time. Other variables evaluated are 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). A child stool sample was planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods. Maternal urine samples were planned to be collected at T3 to investigate pollutants exposure (Phthalates, Bisphenol A and Hydroxypyrene).Results Concerning the birth mode (cesarean section vs. vaginal delivery) significant differences were found only at genera and species levels (T0). A significantly higher relative abundance of Firmicutes was found in meconium of infants born from mothers affected by overweight/obesity, when compared to women with normal weight before pregnancy (T0). Regards type of feeding (breastfed vs formula-fed) the gut microbiota composition differed significantly only at genus and species level (T1).Conclusion These preliminary and explorative results confirmed that pre-pregnancy BMI, mode of delivery and infant factors could affect the infant microbiota composition at different levels.

Download Full-text

Individual differences in members of Actinobacteria, Bacteroidetes, and Firmicutes is associated with resistance or vulnerability to addiction-like behaviors in heterogeneous stock rats

10.1101/2021.07.23.453592 ◽

2021 ◽

Author(s):

Sierra Simpson ◽

Giordano de Guglielmo ◽

Molly Brennan ◽

Lisa Maturin ◽

Greg Peters ◽

...

Keyword(s):

Individual Differences ◽

Gut Microbiome ◽

Metabolic Pathways ◽

Small Sample Size ◽

Small Sample ◽

Self Administration ◽

Drug Induced ◽

Innovative Strategy ◽

Linear Discriminant ◽

Microbiome Composition

An emerging element in psychiatry is the gut-brain-axis, the bi-directional communication pathways between the gut microbiome and the brain. A prominent hypothesis, mostly based on preclinical studies, is that individual differences in the gut microbiome composition and drug- induced dysbiosis may be associated with vulnerability to psychiatric disorders including substance use disorder. However, most studies used small sample size, ignored individual differences, or used animal models with limited relevance to addiction. Here, we test the hypothesis that pre-existing microbiome composition and drug-induced changes in microbiome composition can predict addiction-like behaviors using an advanced animal model of extended access to cocaine self-administration in a large cohort of heterogenous stock (HS) rats. Adult male and female HS rats were allowed to self-administer cocaine under short (2h/day) and long access (6h/day) for ~7 weeks under various schedule of reinforcement to identify individuals that are resistant or vulnerable to addiction-like behaviors and fecal samples were collected before the first session and after the last session to assess differences in the microbiome composition. Linear discriminant analysis (LDA) identified sex-dependent and sex-independent differences at the phylum, order, and species level that are differentially abundant in resistant vs. vulnerable individuals, including high level of actinobacteria both before the first exposure to cocaine and after 7 weeks of cocaine self-administration in resistant animals. Predictions of functional gene content using PICRUSt revealed differential regulation of short-chain fatty acid processing in the vulnerable group after self-administration. These results identify microbiome constituents as well as metabolic pathways that are associated with resistance or vulnerability to addiction-like behaviors in rats. Identification of microbes and tangential metabolic pathways involved in cocaine resilience/vulnerability may represent an innovative strategy for the development of novel biomarkers and medication for the treatment of cocaine use disorder.

Download Full-text

The sugar composition of the fibre in selected plant foods modulates weaning infants’ gut microbiome composition and fermentation metabolites in vitro

Scientific Reports ◽

10.1038/s41598-021-88445-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shanthi G. Parkar ◽

Jovyn K. T. Frost ◽

Doug Rosendale ◽

Halina M. Stoklosinski ◽

Carel M. H. Jobsis ◽

...

Keyword(s):

Gut Microbiome ◽

Gas Production ◽

Sugar Composition ◽

Microbiome Composition ◽

Fibre Concentration ◽

Microbiome Profile ◽

Infant Gut Microbiome ◽

Immune Health ◽

Faecal Bacteria

AbstractEight plant-based foods: oat flour and pureed apple, blackcurrant, carrot, gold- and green-fleshed kiwifruit, pumpkin, sweetcorn, were pre-digested and fermented with pooled inocula of weaning infants’ faecal bacteria in an in vitro hindgut model. Inulin and water were included as controls. The pre-digested foods were analysed for digestion-resistant fibre-derived sugar composition and standardised to the same total fibre concentration prior to fermentation. The food-microbiome interactions were then characterised by measuring microbial acid and gas metabolites, microbial glycosidase activity and determining microbiome structure. At the physiologically relevant time of 10 h of fermentation, the xyloglucan-rich apple and blackcurrant favoured a propiogenic metabolic and microbiome profile with no measurable gas production. Glucose-rich, xyloglucan-poor pumpkin caused the greatest increases in lactate and acetate (indicative of high fermentability) commensurate with increased bifidobacteria. Glucose-rich, xyloglucan-poor oats and sweetcorn, and arabinogalactan-rich carrot also increased lactate and acetate, and were more stimulatory of clostridial families, which are indicative of increased microbial diversity and gut and immune health. Inulin favoured a probiotic-driven consortium, while water supported a proteolytic microbiome. This study shows that the fibre-derived sugar composition of complementary foods may shape infant gut microbiome structure and metabolic activity, at least in vitro.

Download Full-text

Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya

Gut ◽

10.1136/gutjnl-2018-317399 ◽

2018 ◽

Vol 68 (4) ◽

pp. 645-653 ◽

Cited By ~ 9

Author(s):

Daniela Paganini ◽

Mary A Uyoga ◽

Guus A M Kortman ◽

Colin I Cercamondi ◽

Hans C Winkler ◽

...

Keyword(s):

Gut Microbiome ◽

Community Dwelling ◽

Controlled Study ◽

Faecal Calprotectin ◽

Microbiome Composition ◽

E Coli ◽

Increase Risk ◽

Infant Gut Microbiome ◽

Registration Number ◽

Antibiotic Efficacy

ObjectiveMany African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).DesignIn a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8–10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (Fe−Ab+); (C) no antibiotics and iron-MNPs (Fe+Ab−); or (D) no antibiotics and no-iron-MNPs (Fe−Ab−). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5–D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.ResultsIn Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in Fe−Ab+. In Fe−Ab+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In Fe−Ab+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with Fe−Ab+ (12.4%) (p=0.04) and compared with Fe+Ab− (5.2%) (p=0.00).ConclusionOur findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.Trial registration numberNCT02118402; Pre-results.

Download Full-text

Population Pharmacokinetic-Pharmacodynamic Analysis of Anidulafungin in Adult Patients with Fungal Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01473-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 466-474 ◽

Cited By ~ 22

Author(s):

Ping Liu

Keyword(s):

Fungal Infections ◽

Small Sample Size ◽

Safety Data ◽

Area Under The Curve ◽

Positive Association ◽

Disease Status ◽

Small Sample ◽

Adult Patients ◽

Population Pharmacokinetic ◽

Concentration Data

ABSTRACTTo evaluate the exposure-response relationships for efficacy and safety of intravenous anidulafungin in adult patients with fungal infections, a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262 patients in four phase 2/3 studies. The plasma concentration data were fitted with a previously developed population PK model. Anidulafungin exposures in patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on the final PK model. Since the patient population, disease status, and efficacy endpoints varied in these studies, the exposure-efficacy relationship was investigated separately for each study using logistic regression as appropriate. Safety data from three studies (n= 235) were pooled for analysis, and one study was excluded due to concomitant use of amphotericin B as a study treatment and different disease populations. The analysis showed that the same dosing regimen of anidulafungin can be administered to all patients regardless of body weight. Nonetheless, caution should be taken for patients with extremely high weight (e.g., >150 kg). There was a trend of positive association between anidulafungin exposure and efficacy in patients with esophageal candidiasis or invasive candidiasis, including candidemia (ICC); however, adequate characterization of the effect of anidulafungin exposure on response could not be established due to the relatively small sample size. No threshold value for exposure could be established, since patients with low exposure also achieved successful outcomes (e.g., area under the curve < 40 mg · h/liter in ICC patients). There was no association between anidulafungin exposure and the treatment-related adverse events or all-causality hepatic laboratory abnormalities.

Download Full-text

Delivery mode impacts newborn gut colonization efficiency

10.1101/2020.01.29.919993 ◽

2020 ◽

Cited By ~ 2

Author(s):

Caroline Mitchell ◽

Larson Hogstrom ◽

Allison Bryant ◽

Agnes Bergerat ◽

Avital Cher ◽

...

Keyword(s):

Gut Microbiome ◽

Dominant Factor ◽

Delivery Mode ◽

Metagenomic Sequencing ◽

Vaginal Microbiome ◽

Abdominal Incision ◽

Birth Canal ◽

Microbiome Composition ◽

Gut Colonization ◽

Infant Gut Microbiome

AbstractDelivery mode is the variable with the greatest influence on the infant gut microbiome composition in the first few months of life. Children born by Cesarean section (C-section) lack species from the Bacteroides genus in their gut microbial community, and this difference can be detectable until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome, as children born by C-section do not pass through the birth canal; however, Bacteroides species are not common members of the vaginal microbiome, thus this explanation seems inadequate. Here, we set out to re-evaluate this hypothesis by collecting rectal and vaginal samples before delivery from 73 mothers with paired stool from their infants in the first two weeks of life. We compared microbial profiles of infants born by planned, pre-labor C-section to those born by emergent, post-labor surgery (where the child was in the birth canal, but eventually delivered through an abdominal incision), and found no significant differences in the microbiome between these two groups. Both groups showed the characteristic signature lack of Bacteroides species, despite their difference in exposure to the birth canal. Surprisingly, this signature was only evident in samples from week two of life, but not in the first week. Children born by C-section often had high abundance of Bacteroides in their first few days of life, but these were not stable colonizers of the infant gut, as they were not detectable by week two. Finally, we used metagenomic sequencing to compare microbial strains in maternal vaginal and rectal samples and samples from their infants; we found evidence for mother-to-child transmission of rectal rather than vaginal strains. These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.

Download Full-text

Safety and Modulatory Effects of Humanized Galacto-Oligosaccharides on the Gut Microbiome

Frontiers in Nutrition ◽

10.3389/fnut.2021.640100 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jason W. Arnold ◽

Hunter D. Whittington ◽

Suzanne F. Dagher ◽

Jeffery Roach ◽

M. Andrea Azcarate-Peril ◽

...

Keyword(s):

Gut Microbiome ◽

Alpha Diversity ◽

Biological Synthesis ◽

Glycosyl Hydrolases ◽

Microbiome Composition ◽

Metabolic Substrates ◽

Beneficial Impact ◽

Infant Gut Microbiome ◽

Membrane Bound

Complex dietary carbohydrate structures including β(1–4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract and arrive intact to the colon where they benefit the host by selectively stimulating microbial growth. Studies have reported the beneficial impact of GOS (alone or in combination with other prebiotics) by serving as metabolic substrates for modulating the assembly of the infant gut microbiome while reducing GI infections. N-Acetyl-D-lactosamine (LacNAc, Galβ1,4GlcNAc) is found in breast milk as a free disaccharide. This compound is also found as a component of human milk oligosaccharides (HMOs), which have repeating and variably branched lactose and/or LacNAc units, often attached to sialic acid and fucose monosaccharides. Human glycosyl-hydrolases do not degrade most HMOs, indicating that these structures have evolved as natural prebiotics to drive the proper assembly of the infant healthy gut microbiota. Here, we sought to develop a novel enzymatic method for generating LacNAc-enriched GOS, which we refer to as humanized GOS (hGOS). We showed that the membrane-bound β-hexosyl transferase (rBHT) from Hamamotoa (Sporobolomyces) singularis was able to generate GOS and hGOS from lactose and N-Acetyl-glucosamine (GlcNAc). The enzyme catalyzed the regio-selective, repeated addition of galactose from lactose to GlcNAc forming the β-galactosyl linkage at the 4-position of the GlcNAc and at the 1-position of D-galactose generating, in addition to GOS, LacNAc, and Galactosyl-LacNAc trisaccharides which were produced by two sequential transgalactosylations. Humanized GOS is chemically distinct from HMOs, and its effects in vivo have yet to be determined. Thus, we evaluated its safety and demonstrated the prebiotic's ability to modulate the gut microbiome in 6-week-old C57BL/6J mice. Longitudinal analysis of gut microbiome composition of stool samples collected from mice fed a diet containing hGOS for 5 weeks showed a transient reduction in alpha diversity. Differences in microbiome community composition mostly within the Firmicutes phylum were observed between hGOS and GOS, compared to control-fed animals. In sum, our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo, promoting the growth of beneficial microorganisms, including Bifidobacterium and Akkermansia.

Download Full-text

Abstract 609: Plasma Carnitine is Associated with Gut Microbiome Composition, Diet, and Markers of Cardiometabolic Health

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.609 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Holly M Smith ◽

Muredach P Reilly ◽

Jane F Ferguson

Keyword(s):

Gut Microbiome ◽

Illumina Miseq ◽

Cardiometabolic Health ◽

Monounsaturated Fat ◽

Animal Products ◽

Microbiome Composition ◽

Processed Meats ◽

Plasma Carnitine ◽

Refined Carbohydrates ◽

The Relationship

Cardiometabolic health is influenced by both diet and gut microbiome composition, however mechanisms remain unclear. The dietary-derived metabolite carnitine has been of particular interest for its potential gut microbial-mediated relationship to atherosclerosis. Using plasma carnitine as an intermediate probe, we examined the relationship between diet, gut microbiome composition, circulating metabolite levels, and measurements of cardiometabolic health. Samples (blood, stool) and data (diet, anthropometrics) were collected from 136 healthy subjects. Purified stool 16S V4 DNA was sequenced (Illumina MiSeq, 300bp paired-end reads, ~150,000 reads/sample). Plasma carnitine was analyzed by mass spectrometry. There were several dietary components significantly associated with plasma carnitine, with an overall pattern of a diet rich in animal products and refined carbohydrates (dairy, processed meats, non-whole grains and starchy vegetables) associated with higher carnitine, while monounsaturated fat intake was associated with lower carnitine. Plasma carnitine was significantly negatively correlated with several bacterial genera including Blautia (r=-0.3 p=0.001), Parabacteroides (r=-0.2, p=0.03), and Coprococcus (r=-0.389, p<0.001). Carnitine levels above the median were associated with increases in cardiometabolic risk factors including higher systolic blood pressure (SBP, 118 vs 111 mmHg, p=0.014), BMI (27 vs. 24 kg/m 2 , p=0.002), waist-hip ratio (WHR, 0.85 vs 0.8, p=0.001) as well as higher levels of blood components associated with cardiovascular risk, including circulating monocytes (p=0.007) and hemoglobin (p=0.006). Both diet and microbiome composition also associated with several risk markers (WHR, SBP, hemoglobin), albeit to a lesser extent than plasma carnitine. In conclusion, we provide evidence for inter-related relationships between diet, microbiome composition, circulating metabolites, and markers of cardiometabolic health.

Download Full-text

Exploring the Gut Microbiome Alteration of the European Hare (Lepus europaeus) after Short-Term Diet Modifications

Biology ◽

10.3390/biology10020148 ◽

2021 ◽

Vol 10 (2) ◽

pp. 148

Author(s):

Anna Padula ◽

Marina Bambi ◽

Chiara Mengoni ◽

Claudia Greco ◽

Nadia Mucci ◽

...

Keyword(s):

Gut Microbiome ◽

High Sensitivity ◽

Illumina Miseq ◽

Lepus Europaeus ◽

Control Group ◽

Short Term ◽

European Hare ◽

Faecal Pellets ◽

Microbiome Composition ◽

Hypervariable Regions

This study aimed to characterise the gut microbiome composition of European hares (Lepus europaeus) and its potential changes after a short-term diet modification. The high sensitivity of European hare to habitat changes makes this species a good model to analyse possible alterations in gut microbiome after the introduction of additional nourishment into the diet. In total, 20 pairs were chosen for the experiments; 10 pairs formed the control group and were fed with standard fodder. The other 10 pairs represented the experimental group, whose diet was integrated with apples and carrots. The DNA from fresh faecal pellets collected after 4 days from the start of the experiment was extracted and the V3-V4 hypervariable regions were amplified and sequenced using the Illumina MiSeq® platform. The obtained amplicon sequence variants were classified into 735 bacterial genera belonging to 285 families and 36 phyla. The control and the experimental groups appeared to have a homogenous dispersion for the two taxonomic levels analysed with the most abundant phyla represented by Bacteroidetes and Firmicutes. No difference between control and experimental samples was detected, suggesting that the short-term variation in food availability did not alter the hares’ gut microbiome. Further research is needed to estimate significant time threshold.

Download Full-text