Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.

Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.

Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions.

BACKGROUND: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes. METHODS: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments. RESULTS: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels. CONCLUSIONS: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.

Bowel function in a prospective cohort of 1052 healthy term infants up to 4 months of age.

The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9-5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9-3.6, and a median of 1.1, IQR 0.6-1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%).     Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants.

Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.

BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season. METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses. RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile). CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.

Cross-sectional study of the proportion of antibiotic use during childbirth in full-term deliveries in Finland.

PURPOSE: In developed countries, data on the frequency of antibiotics given to mothers during childbirth are limited beyond the overall effect of all various prophylactic indications. Also, data on the impact of such antibiotics to the well-being of term babies are scarce. We aimed to characterize the frequency of antibiotic use during childbirth of term pregnancy. Secondly, we assessed whether the use of antibiotics was associated with any symptoms in infants. METHODS: This was a cross-sectional study of 1019 term deliveries of women participating in the prospective Health and Early Life Microbiota (HELMi) birth cohort study between March 2016 and March 2018 in the capital region of Finland. The data on antibiotic use were collected from the hospital records. RESULTS: In total, 37% of the mothers received antibiotics during childbirth and 100% in Caesarean Sects. (17% of the deliveries). Less than 5% of antibiotics were non-prophylactic. In vaginal deliveries, the most common indication (18%) was prophylaxis for Group B Streptococcus. The most frequently used antibiotics were cefuroxime (22%) and benzylpenicillin (15%), and 56% received only one dose. In infants exposed to antibiotics during delivery, defecation frequency was higher during the first months (p-value < 0.0001- 0.0145), and weight gain was higher at the age of three months (p-value 0.0371). CONCLUSION: More than every third new-born in a developed country is exposed to antibiotics during birth. Our findings support the hypothesis that maternal antibiotics given during birth have an impact on the well-being of the infants. These findings should inform current policies for prophylactic antibiotics in childbirth.

Selective maternal seeding and environment shape the human gut microbiome.

Vertical transmission of bacteria from mother to infant at birth is postulated to initiate a life-long host-microbe symbiosis, playing an important role in early infant development. However, only the tracking of strictly defined unique microbial strains can clarify where the intestinal bacteria come from, how long the initial colonizers persist, and whether colonization by other strains from the environment can replace existing ones. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Only strains from the classes Actinobacteria and Bacteroidia, which are essential components of the infant microbiome, are transmitted from the mother and persist for at least 1 yr. In contrast, maternal strains of Clostridia, a dominant class in the mother's gut microbiome, are not observed in the infant. Caesarean-born infants show a striking lack of maternal transmission at birth. After the first year, strain influx from the family environment occurs and continues even in adulthood. Fathers appear to be more frequently donors of novel strains to other family members than receivers. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time.

Impact of Delivery Mode on Infant Gut Microbiota.

Microbial colonization of the neonate is an important feature of normal birth. The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. During vaginal birth, the infant is exposed to diverse maternal microbes, of which specific faecal microbes colonize the infant's gut. C-section eliminates the infant's contact with maternal microbes, preventing vertical transmission of gut microbes. Consequently, infants are colonized by bacteria from the environment, including potential pathogens from the hospital environment. Recent studies have shown that intrapartum antibiotic exposure has a C-section-like effect on the infant gut microbiota. While the composition of the gut microbiota largely normalizes during the first year of life, epidemiological studies suggest that the aberrant early microbial exposures have long-term immunological and metabolic consequences. Because of the high prevalence of procedures that prevent normal gut microbiota development, effective methods to normalize the gut microbiota of neonates are urgently needed. Even more importantly, attention should be paid to the microbiota imbalance in C-section-born and antibiotic-exposed infants in clinical practice. Breastfeeding and probiotics are particularly important for infants with disrupted gut colonization.

Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort.

BACKGROUND: The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS: Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS: One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS: Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.

Enhanced nutrient supply and intestinal microbiota development in very low birth weight infants.

BACKGROUND: Promoting a healthy intestinal microbiota may have positive effects on short- and long-term outcomes in very low birth weight (VLBW; BW < 1500 g) infants. Nutrient supply influences the intestinal microbiota. METHODS: Fifty VLBW infants were randomized to an intervention group receiving enhanced nutrient supply or a control group. Fecal samples from 45 infants collected between birth and discharge were analyzed using 16S ribosomal RNA (rRNA) amplicon sequencing. RESULTS: There was considerable individual variation in microbiota development. Microbial richness decreased towards discharge in the controls compared to the intervention group. In the intervention group, there was a greater increase in diversity among moderately/very preterm (MVP, gestational age ≥ 28 weeks) infants and a steeper decrease in relative Staphylococcus abundance in extremely preterm (EP, gestational age < 28 weeks) infants as compared to controls. Relative Bifidobacterium abundance tended to increase more in MVP controls compared to the intervention group. Abundance of pathogens was not increased in the intervention group. Higher relative Bifidobacterium abundance was associated with improved weight gain. CONCLUSION: Nutrition may affect richness, diversity, and microbiota composition. There was no increase in relative abundance of pathogens among infants receiving enhanced nutrient supply. Favorable microbiota development was associated with improved weight gain.

Intestinal Microbiota in Hirschsprung Disease.

OBJECTIVES: The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC). METHODS: All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years. RESULTS: The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3-25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples. CONCLUSIONS: Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.

Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana.

BACKGROUND: Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. METHODS: We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. RESULTS: We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). CONCLUSIONS: The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.

Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to Inflammation.

OBJECTIVES: Inflammatory bowel disease (IBD) is considered to result from interplay between host and intestinal microbiota. While IBD in adults has shown to be associated with marked changes in the intestinal microbiota, there are only a few studies in children, and particularly studies focusing on therapeutic responses are lacking. Hence, this prospective study addressed the intestinal microbiota in pediatric IBD especially related to the level of inflammation. METHODS: In total, 68 pediatric patients with IBD and 26 controls provided stool and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis factor-α (anti-TNF-α). Blood inflammatory markers and fecal calprotectin levels were determined. The intestinal microbiota was characterized by phylogenetic microarray and qPCR analysis. RESULTS: The microbiota varied along a gradient of increasing intestinal inflammation (indicated by calprotectin levels), which was associated with reduced microbial richness, abundance of butyrate producers, and relative abundance of Gram-positive bacteria (especially Clostridium clusters IV and XIVa). A significant association between microbiota composition and inflammation was indicated by a set of bacterial groups predicting the calprotectin levels (area under curve (AUC) of 0.85). During the induction of anti-TNF-α, the microbial diversity and similarity to the microbiota of controls increased in the responder group by week 6, but not in the non-responders (P<0.01; response related to calprotectin levels). The abundance of six groups of bacteria including those related to Eubacterium rectale and Bifidobacterium spp. predicted the response to anti-TNF-α medication. CONCLUSIONS: Intestinal microbiota represents a potential biomarker for correlating the level of inflammation and therapeutic responses to be further validated.

Predator-vole interactions in Northern Europe: the role of small mustelids revised.

The cyclic population dynamics of vole and predator communities is a key phenomenon in northern ecosystems, and it appears to be influenced by climate change. Reports of collapsing rodent cycles have attributed the changes to warmer winters, which weaken the interaction between voles and their specialist subnivean predators. Using population data collected throughout Finland during 1986-2011, we analyse the spatio-temporal variation in the interactions between populations of voles and specialist, generalist and avian predators, and investigate by simulations the roles of the different predators in the vole cycle. We test the hypothesis that vole population cyclicity is dependent on predator-prey interactions during winter. Our results support the importance of the small mustelids for the vole cycle. However, weakening specialist predation during winters, or an increase in generalist predation, was not associated with the loss of cyclicity. Strengthening of delayed density dependence coincided with strengthening small mustelid influence on the summer population growth rates of voles. In conclusion, a strong impact of small mustelids during summers appears highly influential to vole population dynamics, and deteriorating winter conditions are not a viable explanation for collapsing small mammal population cycles.

Utility of an online well-being assessment in targeting employee well-being programmes: a cross-sectional survey study in Finland.

OBJECTIVES: Occupational health challenges are changing, emphasising the need for a more comprehensive approach. This study examines how a subjective well-being assessment can be used to identify target groups for work well-being interventions and brings insight into how survey-based well-being evaluations are linked to clinical health indicators (ie, anthropometric measurements and blood tests). DESIGN: A cross-sectional survey study using results from the Virta1 randomised controlled trial and a third-party well-being questionnaire database. SETTING AND PARTICIPANTS: Online well-being survey data from 2990 respondents was used to identify target groups for work well-being interventions and clinical health indicator data from 713 respondents was used to examine how subjective evaluations are linked to physical health. RESULTS: We identified five groups of employees with different well-being challenges and presenteeism levels: Good well-being, Hard on oneself, Lifestyle challenges, Recovery challenges and Multiple challenges. The subjective evaluations correlated with clinical health indicators, showing that the well-being groups differed significantly in their average clinical health profiles. Especially people in the Multiple challenges group had multiple physical health challenges, while people in the Good well-being and Hard on oneself groups did not. CONCLUSIONS: Our results show that a subjective well-being assessment can identify different groups with distinct characteristics and health risks and that subjective evaluations of well-being correlate strongly with physical health. Online well-being assessment offers potentially a cost-effective way for occupational health providers to screen large populations to target physical health examinations to groups that need them the most and simultaneously get a better understanding of their well-being needs.

Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).

Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.

BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

Paternal and induced gut microbiota seeding complement mother-to-infant transmission.

Microbial colonization of the neonatal gut involves maternal seeding, which is partially disrupted in cesarean-born infants and after intrapartum antibiotic prophylaxis. However, other physically close individuals could complement such seeding. To assess the role of both parents and of induced seeding, we analyzed two longitudinal metagenomic datasets (health and early life microbiota [HELMi]: N = 74 infants, 398 samples, and SECFLOR: N = 7 infants, 35 samples) with cesarean-born infants who received maternal fecal microbiota transplantation (FMT). We found that the father constitutes a stable source of strains for the infant independently of the delivery mode, with the cumulative contribution becoming comparable to that of the mother after 1 year. Maternal FMT increased mother-infant strain sharing in cesarean-born infants, raising the average bacterial empirical growth rate while reducing pathogen colonization. Overall, our results indicate that maternal seeding is partly complemented by that of the father and support the potential of induced seeding to restore potential deviations in this process.

Different measures of body weight as predictors of sickness absence.

AIMS: Excessive weight is associated with increased sickness absence from work due to obesity-linked health problems. However, it is not known which obesity measure best predicts sickness absence. First, we aimed to compare body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) as predictors of sickness absence spells of various lengths. Second, we aimed to compare BMI based on self-reported and measured weight and height as a predictor of sickness absence to assess the validity of self-reported BMI. METHODS: The participants were 5750 employees of the City of Helsinki, aged 40-60 years, who were followed up on average for 4.8 years using the employer's register. Sickness absence spells were classified as self-certified short (1-3 days), medically certified medium length (4-14 days), and long (>14 days) absence spells. RESULTS: All measures of body weight predicted sickness absence. The relative rates of long sickness absence in the highest quintile as compared to the lowest quintile varied in women from 1.62 (95% CI 1.35-1.94) to 1.89 (95% CI 1.62-2.23) and in men from 1.40 (95% CI 0.76-2.59) to 2.33 (95% CI 1.32-4.11). Differences in the predictive power of BMI and WC were small: both were more strongly associated with sickness absence than WHR. Self-reported BMI performed equally well as measured BMI. CONCLUSIONS: BMI - measured or self-reported - is a valid anthropometric indicator of body weight and predictor of obesity-associated health-risks. Its use is feasible for research purposes as well as for the assessment of weight-related risks to work ability.

Sources of gut microbiota variation in a large longitudinal Finnish infant cohort.

BACKGROUND: Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota determinants including technical variables has not been performed in large infant cohorts. METHODS: We studied the effect of 109 variables on the 16S rRNA gene amplicon-based gut microbiota profiles of infants sampled longitudinally from three weeks to two years of life in the Finnish HELMi birth cohort. Spot faecal samples from both parents were included for intra-family analyses, totalling to 7657 samples from 985 families that were evaluated for beta-diversity patterns using permutational multivariate analysis on Bray-Curtis distances, and differential abundance testing and alpha-diversity for variables of interest. We also assessed the effect of different taxonomic levels and distance methods. FINDINGS: In time point-specific models, the largest share of variation explained, up to 2-6%, were seen in decreasing order for the DNA extraction batch, delivery mode and related perinatal exposures, defecation frequency and parity/siblings. Variables describing the infant gastrointestinal function were continuously important during the first two years, reflecting changes in e.g., feeding habits. The effect of parity/siblings on infant microbiota was modified by birth mode and exposure to intrapartum antibiotics, exemplifying the tight interlinkage of perinatal factors relevant for infant microbiota research. In total, up to 19% of the biological microbiota variation in the infant gut could be explained. Our results highlight the need to interpret variance partitioning results in the context of each cohort's characteristics and microbiota processing. INTERPRETATION: Our study provides a comprehensive report of key factors associated with infant gut microbiota composition across the two first years of life in a homogenous cohort. The study highlights possible important future research areas and confounding factors to be considered. FUNDING: This research was supported by Business Finland, Academy of Finland, Foundation for Nutrition Research and the Doctoral Program in Microbiology and Biotechnology, University of Helsinki, Finland.

Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease.

BACKGROUND: The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease. METHODS: We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts. RESULTS: At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline. CONCLUSIONS: High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.

We studied absolute and relative abundances of fecal microbiota in relation to response to induction therapy with infliximab in pediatric inflammatory bowel disease. We discovered that a high absolute abundance of anti-inflammatory Bifidobacteriales at baseline associated with response.