| 1. |
- Kostic, Aleksandar D., et al.
(författare)
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The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes
- 2015
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Ingår i: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 17:2, s. 260-273
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Tidskriftsartikel (refereegranskat)abstract
- Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.
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| 2. |
- Lamichhane, Santosh, et al.
(författare)
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Dysregulation of secondary bile acid metabolism precedes islet autoimmunity and type 1 diabetes
- 2022
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Ingår i: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 3:10
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool BAs in longitudinal samples collected at 3, 6, 12, 18, 24, and 36 months of age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple islet AAbs (P2Ab; n = 13) and controls (CTRs; n = 38) who remained AAb negative. We also analyzed the stool microbiome in a subgroup of these children. Factor analysis showed that age had the strongest impact on both BA and microbiome profiles. We found that at an early age, systemic BAs and microbial secondary BA pathways were altered in the P2Ab group compared with the P1Ab and CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.
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| 3. |
- Lamichhane, Santosh, et al.
(författare)
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Impact of exposure to per- and polyfluoroalkyl substances on fecal microbiota composition in mother-infant dyads
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence suggesting that chemical exposure alters gut microbiota composition. However, not much is known about the impact of per- and polyfluoroalkyl substances (PFAS) on the gut microbial community. Here, in a mother-infant study, we set out to identify the gut bacterial species that associate with chemical exposure before (maternal) and after (maternal, infant) birth. Paired serum and stool samples were collected from mother-infant dyads (n = 30) in a longitudinal setting. PFAS were quantified in maternal serum to examine their associations with the microbial compositions (determined by shotgun metagenomic sequencing) in mothers and infants. High maternal exposure to PFAS was consistently associated with increased abundance of Methanobrevibacter smithii in maternal stool. Among individual PFAS compounds, PFOS and PFHpS showed the strongest association with M. smithii. However, maternal total PFAS exposure associated only weakly with the infant microbiome. Our findings suggest that PFAS exposure affects the composition of the adult gut microbiome.
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| 4. |
- Larsson, Stefan, et al.
(författare)
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Feeding of wild and hatchery reared Atlantic salmon (Salmo salar L.) smolts during downstream migration
- 2011
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Ingår i: Environmental Biology of Fishes. - : Kluwer Journals Online. - 0378-1909 .- 1573-5133. ; 92:3, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- In general, hatchery salmonid smolts experience higher mortality during migration than wild smolts, which is suggested to be due to domestication effects and that hatchery fish lack experience of the natural environment. However, possible differences in feeding during smolt migration between hatchery and wild smolts have rarely been addressed. We compared the number of feeding smolts and stomach fullness among wild Atlantic salmon smolts, hatchery-reared smolts released as 1-year-old parr, and hatchery-reared smolts released as 2-year-old smolts during their descent to sea in River Tornionjoki. In addition, estimations of prey selection among the smolt groups were conducted. A high proportion of wild smolts and smolts stocked as parr actively fed during the smolt migration. A lower proportion of smolts stocked as smolts was feeding and their stomach fullness were much reduced in comparison with the two other groups. The study also indicated that the feeding of migrating smolts is selective rather than opportunistic. In conclusion, this study suggests that stocked 2-year-old smolts may enter sea with an inferior foraging behaviour and it is a possibility that this may contribute to the observed low post-smolt survival in the Baltic Sea.
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| 5. |
- Leong, Karen S. W., et al.
(författare)
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Effects of Fecal Microbiome Transfer in Adolescents With Obesity The Gut Bugs Randomized Controlled Trial
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- Importance Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.
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| 6. |
- Leong, Karen S. W., et al.
(författare)
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High prevalence of undiagnosed comorbidities among adolescents with obesity
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic diseases are increasing among adolescents with obesity. Although the reported prevalence of metabolic syndrome is approximately 30% worldwide, its prevalence is largely unknown among New Zealand adolescents. Therefore, we assessed the health of adolescents with obesity (BMI ≥ 30 kg/m2) enrolled in a randomised clinical trial (Gut Bugs Trial), to identify the prevalence of undiagnosed comorbidities. Assessments included anthropometry, 24-h ambulatory blood pressure monitoring, and insulin sensitivity. We report on baseline data (pre-randomisation) on 87 participants (14–18 years; 59% females), with mean BMI 36.9 ± 5.3 kg/m2 (BMI SDS 3.33 ± 0.79). Approximately 40% of participants had undiagnosed metabolic syndrome, which was twice as common among males. Half (53%) had pre-diabetes and 92% a reduction in insulin sensitivity. Moreover, 31% had pre-hypertension/hypertension, 69% dyslipidaemia, and 25% abnormal liver function. Participants with class III obesity had a greater risk of metabolic syndrome than those with classes I/II [relative risk 1.99 (95% CI 1.19, 3.34)]. Risks for pre-hypertension/hypertension and inflammation were also greater among those with class III obesity. We identified a high prevalence of undiagnosed comorbidities among adolescents with obesity in New Zealand. As adolescent obesity tracks into adulthood, early interventions are needed to prevent progression to overt cardiometabolic diseases.
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| 7. |
- Stewart, Christopher J., et al.
(författare)
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Temporal development of the gut microbiome in early childhood from the TEDDY study
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7728, s. 583-588
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Tidskriftsartikel (refereegranskat)abstract
- The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1–9 such as persistent islet autoimmunity and type 1 diabetes10–12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months 15–30), and a stable phase (months 31–46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case–control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial–immune crosstalk for long-term health.
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| 8. |
- Vatanen, Tommi, et al.
(författare)
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The human gut microbiome in early-onset type 1 diabetes from the TEDDY study
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7728, s. 589-594
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.
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| 9. |
- Wilson, Brooke C., et al.
(författare)
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Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section : A pilot randomised placebo-controlled trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 69
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Tidskriftsartikel (refereegranskat)abstract
- Background: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257).Methods: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CSseeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events.Findings: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment.Interpretation: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome.
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