Calypso is an easy-to-use online software suite that allows non-expert users to mine, interpret and compare taxonomic information from metagenomic or 16S rDNA datasets. Calypso has a focus on ...multivariate statistical approaches that can identify complex environment-microbiome associations. The software enables quantitative visualizations, statistical testing, multivariate analysis, supervised learning, factor analysis, multivariable regression, network analysis and diversity estimates. Comprehensive help pages, tutorials and videos are provided via a wiki page.
The web-interface is accessible via http://cgenome.net/calypso/ . The software is programmed in Java, PERL and R and the source code is available from Zenodo ( https://zenodo.org/record/50931 ). The software is freely available for non-commercial users.
l.krause@uq.edu.au.
Supplementary data are available at Bioinformatics online.
The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the ...effect of mainly 2'-fucosyllactose (2'-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother's milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow's milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs.
Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled ...multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2'-fucosyllactose and lacto-N-
tetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (
= 58) appeared closer to that of BF (
= 35) than control (
= 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for
at high abundance) than in the other (FCT Bi for
). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.)
Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.
We found that the relatively simple microbiota of young infants shifts predictably to a more mature anaerobic microbiota during infancy and the dynamics of this shift are influenced by environmental ...factors. In this longitudinal study of 75 infants, we demonstrate high interindividual variability within the normal range of birth outcomes, especially in the rate of microbiota progression. Most had acquired a microbiota profile high in Bifidobacterium and Collinsella by 6 months of age, but the time point of this acquisition was later in infants delivered by caesarean section and those born after a shorter duration of gestation. Independently of the delivery mode and gestation duration, infants who acquired a profile high in Bifidobacterium and Collinsella at a later age had lower adiposity at 18 months of age.
This study shows that the acquisition of the early microbiota is strongly influenced by environmental factors such as the delivery mode and duration of gestation, even in healthy neonates. The composition of the early microbiota has been linked with long-lasting effects on health and disease. Here we show that the rate of acquisition of certain microbiota predicts adiposity at 18 months of age and so potentially the risk of later obesity.
Abstract The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene ...transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3×109 and 3×107 plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in ...diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative.
...T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli titers and enteropathogens were determined in stool and quantitative diarrhea parameters (stool output, stool frequency) were measured. Stool microbiota was studied by 16S rRNA gene sequencing; the genomes of four fecal Streptococcus isolates were sequenced.
No adverse events attributable to oral phage application were observed (primary safety outcome). Fecal coliphage was increased in treated over control children, but the titers did not show substantial intestinal phage replication (secondary microbiology outcome). 60% of the children suffered from a microbiologically proven E. coli diarrhea; the most frequent diagnosis was ETEC infections. Bacterial co-pathogens were also detected. Half of the patients contained phage-susceptible E. coli colonies in the stool. E. coli represented less than 5% of fecal bacteria. Stool ETEC titers showed only a short-lived peak and were otherwise close to the replication threshold determined for T4 phage in vitro. An interim analysis after the enrollment of 120 patients showed no amelioration in quantitative diarrhea parameter by PT over standard care (tertiary clinical outcome). Stool microbiota was characterized by an overgrowth with Streptococcus belonging to the Streptococcus gallolyticus and Streptococcus salivarius species groups, their abundance correlated with quantitative diarrhea outcome, but genome sequencing did not identify virulence genes.
Oral coliphages showed a safe gut transit in children, but failed to achieve intestinal amplification and to improve diarrhea outcome, possibly due to insufficient phage coverage and too low E. coli pathogen titers requiring higher oral phage doses. More knowledge is needed on in vivo phage–bacterium interaction and the role of E. coli in childhood diarrhea for successful PT.
The study was supported by a grant from Nestlé Nutrition and Nestlé Health Science. The trial was registered with Identifier NCT00937274 at ClinicalTrials.gov.
•Coliphages given orally to children with bacterial diarrhea appeared in the stool, but did not improve clinical outcome.•In microbiologically diagnosed E. coli diarrhea, pathogen titers were close to the replication threshold of coliphages.•Acute bacterial diarrhea displayed a marked dysbiosis with fecal streptococci that stabilized with recovery from diarrhea.
Antibiotic resistance of bacterial infections reached alarming levels. Phage therapy is a potential alternative antimicrobial. We demonstrated that two different oral phage preparations did not improve acute bacterial diarrhea in children from Bangladesh. We observed fecal excretion of the oral phage, but no major phage amplification in the gut. E. coli pathogen levels were low and the fecal microbiota showed a transient overgrowth with streptococci. Future phage trials should first verify the titer and association of the targeted pathogen with the disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Our study is the first to compare the nasopharyngeal microbiota of pediatric pneumonia patients and control children by 454 pyrosequencing. A distinct microbiota was associated with different ...pneumonia etiologies. Viral pneumonia was associated with a high abundance of the operational taxonomic unit (OTU) corresponding to Moraxella lacunata. Patients with nonviral pneumonia showed high abundances of OTUs of three typical bacterial pathogens, Streptococcus pneumoniae complex, Haemophilus influenzae complex, and Moraxella catarrhalis. Patients classified as having no definitive etiology harbored microbiota particularly enriched in the H. influenzae complex. We did not observe a commensal taxon specifically associated with health. The microbiota of the healthy nasopharynx was more diverse and contained a wider range of less abundant taxa.
Cow's milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA ...until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2'-fucosyllactose (2'-FL) and lacto-
-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.
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