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Children growing up on farms or with pets have a lower risk of developing allergy, which may be linked to their gut microbiota development during infancy. Children from the FARMFLORA birth cohort (N = 65), of whom 28 (43%) lived on a dairy farm and 40 (62%) had pets, provided fecal samples at intervals from 3 days to 18 months of age. Gut microbiota composition was characterized using quantitative microbial culture of various typical anaerobic and facultatively anaerobic bacteria, with colonization rate and population counts of bacterial groups determined at the genus or species level. Allergy was diagnosed at three and eight years of age by experienced pediatricians. Generalized estimating equations were used to identify associations between farm residence or pet ownership, gut microbiota development and allergy. Adjustments were made for important potential confounders. Growing up on a farm was associated with a higher ratio of anaerobic to facultative bacteria in the first week, smaller Escherichia coli populations in colonized children in the first months of life and less frequent colonization by Clostridioides difficile at 12 months of age. Having pets in the household was associated with more frequent colonization by Bifidobacterium, Lactobacillus and Bacteroides in the first months. A higher ratio of anaerobic to facultative bacteria at one week of age, early colonization by Bifidobacterium, Lactobacillus and Bacteroides, and reduced carriage of C. difficile at 4-12 months of age all correlated negatively with subsequent allergy diagnosis. Our findings indicate that lower rates of allergy in children growing up on farms or with pets may be related to early establishment of typical anaerobic commensals in their gut microbiota. However, further studies are needed to validate our observations in this small birth cohort study.

Background The gut microbiota may influence immune maturation during infancy. While cesarean delivery is known to delay acquisition of a mature anaerobic microbiota, the influence of being firstborn on early gut colonization is less well studied. Methods Feces were collected regularly from 3 days to 18 months of age in the FARMFLORA cohort ( N  = 65) and cultured quantitatively for major anaerobic and facultative bacteria. Colonization rates and population counts of different gut bacteria were analyzed in relation to birth order, delivery mode, and antibiotic exposure during delivery. Each exposure was adjusted for the other two. Results Birth order, delivery mode and antibiotic exposure were each independently associated with gut colonization. Firstborn infants ( N  = 29) acquired Escherichia coli and bifidobacteria later than infants with older sibings ( N  = 36) and had signs of microbiota immaturity, including higher levels of facultative bacteria and increased carriage of opportunistic colonizers such as Clostridioides difficile and Staphylococcus aureus . Cesarean-delivered infants ( N  = 10) showed delayed E. coli acquisition and increased colonization by other enterobacteria, while antibiotic exposure during delivery ( N  = 10) delayed colonization by Bacteroides . Conclusions Delayed colonization by typical fecal bacteria in firstborn infants suggests reduced maternal bacterial transfer during delivery. This might contribute to the predilection of firstborn children to develop allergy.

Staphylococcus aureus colonizes the anterior nares, and also the gut, particularly in infants. S. aureus is divided into lineages, termed clonal complexes (CCs), which comprise closely related sequence types (STs). While CC30 and CC45 predominate among nasal commensals, their prevalence among gut-colonizing S. aureus is unknown. Here, 67 gut commensal S. aureus strains from 49 healthy Swedish infants (aged 3 days to 12 months) were subjected to multi-locus sequence typing. The STs of these strains were related to their virulence gene profiles, time of persistence in the microbiota, and fecal population counts. Three STs predominated: ST45 (22% of the strains); ST15 (21%); and ST30 (18%). In a logistic regression, ST45 strains showed higher fecal population counts than the others, independent of virulence gene carriage. The lower fecal counts of ST15 were linked to the carriage of fib genes (encoding fibrinogen-binding proteins), while those of ST30 were linked to fib and sea (enterotoxin A) carriage. While only 11% of the ST15 and ST30 strains were acquired after 2 months of age, this was true of 53% of the ST45 strains ( p  = 0.008), indicating that the former may be less fit for establishment in a more mature microbiota. None of the ST45 strains was transient (persisting < 3 weeks), and persistent ST45 strains colonized for significantly longer periods than persistent strains of other STs (mean, 34 vs 22 weeks, p  = 0.04). Our results suggest that ST45 strains are well-adapted for commensal gut colonization in infants, reflecting yet-unidentified traits of these strains.

Escherichia coli strains segregate into 4 phylogenetic groups, designated “A,” “B1,” “B2,” and “D.” Pathogenic strains belong to group B2 and, to a lesser extent, group D, which more frequently carry virulence-factor genes than do group A strains and group B1 strains. This study investigated whether the capacity of E. coli to persist in the human intestine is related to its phylogenetic type. Resident (n=58) and transient (n=19) commensal E. coli strains isolated during a longitudinal study of 70 Swedish infants and previously tested for virulence-factor–gene carriage were tested for phylogenetic type. Of the strains resident in the intestinal microflora, 60% belonged to group B2, compared with only 21% of the transient strains (P=.004). In logistic regression, group B2 type predicted persistence in the intestinal microflora, independent of carriage of all investigated virulence-factor genes, including genes for P fimbriae (P=.03). Thus, group B2 strains appear to possess yet unidentified traits that enhance their survival in the human intestine

Staphylococcus aureus is a pathogen and a skin commensal that is today also common in the infant gut flora. We examine the role of S. aureus virulence factors for gut colonization. S. aureus isolated from quantitative stool cultures of 49 Swedish infants followed from birth to 12 months of age were assessed for 30 virulence-associated genes, spa type, and agr allele by serial polymerase chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher stool counts than strains lacking these genes, whereas genes for S. aureus enterotoxin A (SEA) were associated with low counts. A cluster of strains belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin-binding protein were all long-time colonizers. Thus, certain S. aureus virulence factors might promote gut colonization.

Children growing up on farms or with pets have a lower risk of developing allergy, which may be linked to their gut microbiota development during infancy. Children from the FARMFLORA birth cohort (N = 65), of whom 28 (43%) lived on a dairy farm and 40 (62%) had pets, provided fecal samples at intervals from 3 days to 18 months of age. Gut microbiota composition was characterized using quantitative microbial culture of various typical anaerobic and facultatively anaerobic bacteria, with colonization rate and population counts of bacterial groups determined at the genus or species level. Allergy was diagnosed at three and eight years of age by experienced pediatricians. Generalized estimating equations were used to identify associations between farm residence or pet ownership, gut microbiota development and allergy. Adjustments were made for important potential confounders. Growing up on a farm was associated with a higher ratio of anaerobic to facultative bacteria in the first week, smaller Escherichia coli populations in colonized children in the first months of life and less frequent colonization by Clostridioides difficile at 12 months of age. Having pets in the household was associated with more frequent colonization by Bifidobacterium, Lactobacillus and Bacteroides in the first months. A higher ratio of anaerobic to facultative bacteria at one week of age, early colonization by Bifidobacterium, Lactobacillus and Bacteroides, and reduced carriage of C. difficile at 4-12 months of age all correlated negatively with subsequent allergy diagnosis. Our findings indicate that lower rates of allergy in children growing up on farms or with pets may be related to early establishment of typical anaerobic commensals in their gut microbiota. However, further studies are needed to validate our observations in this small birth cohort study.

Children growing up on farms or with pets have a lower risk of developing allergy, which may be linked to their gut microbiota development during infancy. Children from the FARMFLORA birth cohort (N = 65), of whom 28 (43%) lived on a dairy farm and 40 (62%) had pets, provided fecal samples at intervals from 3 days to 18 months of age. Gut microbiota composition was characterized using quantitative microbial culture of various typical anaerobic and facultatively anaerobic bacteria, with colonization rate and population counts of bacterial groups determined at the genus or species level. Allergy was diagnosed at three and eight years of age by experienced pediatricians. Generalized estimating equations were used to identify associations between farm residence or pet ownership, gut microbiota development and allergy. Adjustments were made for important potential confounders. Growing up on a farm was associated with a higher ratio of anaerobic to facultative bacteria in the first week, smaller Escherichia coli populations in colonized children in the first months of life and less frequent colonization by Clostridioides difficile at 12 months of age. Having pets in the household was associated with more frequent colonization by Bifidobacterium, Lactobacillus and Bacteroides in the first months. A higher ratio of anaerobic to facultative bacteria at one week of age, early colonization by Bifidobacterium, Lactobacillus and Bacteroides, and reduced carriage of C. difficile at 4-12 months of age all correlated negatively with subsequent allergy diagnosis. Our findings indicate that lower rates of allergy in children growing up on farms or with pets may be related to early establishment of typical anaerobic commensals in their gut microbiota. However, further studies are needed to validate our observations in this small birth cohort study.

Despite extensive literature on the pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal in healthy hosts. Based on two detailed longitudinal datasets on the gut microbiota of healthy adult individuals followed over months to years in France and in the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and the ability to remain in the host (residence). Major E. coli lineages (phylogroups) exhibited similar fitness but a diversity of strategies, from strong colonizers residing for a few days in the gut, to poor colonizers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity resided for longest in hosts. Moreover, the residence time of a strain was reduced more strongly when it competed with other strains of the same phylogroup than of different phylogroups, suggesting niche differentiation between them. To investigate the consequences of the trade-off and niche differentiation for coexistence between strains, we developed a discrete-state Markov model describing the dynamics of E. coli in a population of hosts. We found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms enabling the coexistence of phylogroups over extended periods of time. Our model predicted that a reduction in transmission (e.g. better hygiene) would not alter the balance between phylogroups, while disturbance of the microbiome (e.g. antibiotics) would hinder residents strains such as those of the extra-intestinal pathogenic phylogroup B2.3.

Staphylococcus aureus is both a component of the normal skin flora and an important pathogen. It expresses a range of recognized and putative virulence factors, such as enterotoxins with superantigenic properties. Several superantigen genes, i.e., seg , sei , selm , seln , and selo , are encoded by the enterotoxin gene cluster ( egc ), which is found in the majority of S. aureus isolates. Carriage of egc is associated with fitness of S. aureus in the gut microbiota, but it is not known if it contributes to pathogenicity. We constructed egc + (functional for the seg , selm , and selo genes) and isogenic egc − S. aureus mutants, and investigated their virulence profiles in murine infection models. No effect of egc was seen in a local skin and soft tissue infection model, but in an invasive infection model, increased weight loss was observed after infection with the egc + as compared to the egc − mutant. Mortality and arthritis were not affected by egc status. Our data suggest that egc has limited effects on the virulence of S. aureus . It may primarily function as a colonization factor increasing commensal fitness, although it might have some aggravating effects on the infection when the bacteria reach the blood.