To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.
Longitudinal birth cohort study.
A total of 11 ...532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992.
Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years).
Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass.
Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.
o assess associations of caesarean section with body mass from birth through adolescence.
ongitudinal birth cohort study, following subjects up to 15 years of age.
Children born in 1991-1992 in Avon, ...UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219).
standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI: 85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years.
Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak.
Cesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.
The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked ...a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes
and
Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.
A unified initiative to harness Earth's microbiomes Alivisatos, A. P.; Blaser, M. J.; Brodie, E. L. ...
Science (American Association for the Advancement of Science),
10/2015, Letnik:
350, Številka:
6260
Journal Article
Recenzirano
Odprti dostop
Despite their centrality to life on Earth, we know little about how microbes (1) interact with each other, their hosts, or their environment. Although DNA sequencing technologies have enabled a new ...view of the ubiquity and diversity of microorganisms, this has mainly yielded snapshots that shed limited light on microbial functions or community dynamics. Given that nearly every habitat and organism hosts a diverse constellation of microorganisms-its "microbiome"-such knowledge could transform our understanding of the world and launch innovations in agriculture, energy, health, the environment, and more (see the photo). We propose an interdisciplinary Unified Microbiome Initiative (UMI) to discover and advance tools to understand and harness the capabilities of Earth's microbial ecosystems. The impacts of oceans and soil microbes on atmospheric CO2 are critical for understanding climate change (2). By manipulating interactions at the root-soil-microbe interface, we may reduce agricultural pesticide, fertilizer, and water use enrich marginal land and rehabilitate degraded soils. Microbes can degrade plant cell walls (for biofuels), and synthesize myriad small molecules for new bioproducts, including antibiotics (3). Restoring normal human microbial ecosystems can save lives e.g., fecal microbiome transplantation for Clostridium difficile infections (4). Rational management of microbial communities in and around us has implications for asthma, diabetes, obesity, infectious diseases, psychiatric illnesses, and other afflictions (5, 6). The human microbiome is a target and a source for new drugs (7) and an essential tool for precision medicine (8).
Campylobacter fetus can cause intestinal illness and, occasionally, severe systemic infections. Infections mainly affect persons at higher risk, including elderly and immunocompromised individuals ...and those with occupational exposure to infected animals. Outbreaks are infrequent but have provided insight into sources. Source attribution of sporadic cases through case-control interviews has not been reported. The reservoirs for C. fetus are mainly cattle and sheep. Products from these animals are suspected as sources for human infections. Campylobacter fetus is rarely isolated from food, albeit selective isolation methods used in food microbiology are not suited for its detection. We hypothesize that the general population is regularly exposed to C. fetus through foods of animal origin, cross-contaminated foodstuffs, and perhaps other, as yet unidentified, routes. Campylobacter fetus infection should be suspected particularly in patients with nonspecific febrile illness who are immunocompromised or who may have been occupationally exposed to ruminants.
The prevalence of celiac disease (CD) has increased in recent decades without a clear explanation. The "hygiene hypothesis" theorizes that decreased exposure to bacterial antigens may trigger ...autoimmunity. We aimed to determine whether Helicobacter pylori infection and CD were associated among patients undergoing upper gastrointestinal endoscopy. We performed a cross-sectional study of patients who underwent esophagogastroduodenoscopy with submission of gastric and duodenal biopsies to Miraca Life Sciences, Inc. (Irving, Texas), a US commercial pathology laboratory, during a 4.5-year period (January 2008-June 2012). We compared the prevalence of H. pylori in CD patients with that in persons without CD. We performed multiple logistic regression analysis, adjusting odds ratios for patient age, gender, and racial, ethnic, and socioeconomic factors. Among 136,179 patients, a total of 2,689 (2.0%) had CD. H. pylori prevalence was significantly lower in patients with CD (4.4%) than in those without CD (8.8%; P < 0.0001). After adjustment for the above covariates, this inverse relationship remained strong (adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.40, 0.58). The relationships were similar in men (unadjusted OR = 0.51, 95% CI: 0.38, 0.69) and women (unadjusted OR = 0.46, 95% CI: 0.36, 0.58) and in all age groups. We conclude that H. pylori presence and CD are inversely associated, a relationship that persists after adjustment for socioeconomic factors. Future studies should address whether H. pylori modulates immune responses to ingested gluten.
Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between ...treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.
Are we using too many antibiotics during pregnancy? Ledger, WJ; Blaser, MJ
BJOG : an international journal of obstetrics and gynaecology,
November 2013, 2013-Nov, 2013-11-00, 20131101, Letnik:
120, Številka:
12
Journal Article
Background. Few studies have evaluated the potential influence of Helicobacter pylori on biomarkers for diabetes. Methods. We conducted cross-sectional analyses using data from 7417 participants in ...the National Health and Nutrition Examination Survey (NHANES) III (aged ≥18 years) and 6072 participants in NHANES 1999—2000 (aged ≥3 years) to assess the association between H. pylori and levels of glycosylated hemoglobin (HbA1c). Results. There was no association between H. pylori and history of self-reported diabetes. Helicobacter pylori seropositivity, especially H. pylori cagA positivity, was positively associated (P < .01, NHANES III; P = .02, NHANES 1999—2000) with HbA1c levels after excluding individuals with history of diabetes and controlling for potential confounders. There was also a synergistic interaction between H. pylori and higher body mass index (BMI), such that increased levels of HbA1c associated with having both H. pylori and higher BMI were greater than the sum of their individual effects (P for interaction < .01). This interaction was observed consistently in both NHANES III and NHANES 1999—2000 and for H. pylori cagA positivity in NHANES III. Conclusions. The findings indicate a role of H. pylori in impaired glucose tolerance in adults that may be potentiated by higher BMI level.
The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, ...data on antibiotic use as a risk factor for subsequent CD development are scarce.
In this population-based case-control study we linked nationwide histopathology data on 2,933 individuals with CD (Marsh stage 3; villous atrophy) to the Swedish Prescribed Drug Register to examine the association between use of systemic antibiotics and subsequent CD. We also examined the association between antibiotic use in 2,118 individuals with inflammation (Marsh 1-2) and in 620 individuals with normal mucosa (Marsh 0) but positive CD serology. All individuals undergoing biopsy were matched for age and sex with 28,262 controls from the population.
Antibiotic use was associated with CD (Odds ratio OR = 1.40; 95% confidence interval CI = 1.27-1.53), inflammation (OR = 1.90; 95% CI = 1.72-2.10) and normal mucosa with positive CD serology (OR = 1.58; 95% CI = 1.30-1.92). ORs for prior antibiotic use in CD were similar when we excluded antibiotic use in the last year (OR = 1.30; 95% CI = 1.08-1.56) or restricted to individuals without comorbidity (OR = 1.30; 95% CI = 1.16 - 1.46).
The positive association between antibiotic use and subsequent CD but also with lesions that may represent early CD suggests that intestinal dysbiosis may play a role in the pathogenesis of CD. However, non-causal explanations for this positive association cannot be excluded.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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