Erratum: Gut resistome development in healthy twin pairs in the first year of life.

[This corrects the article DOI: 10.1186/s40168-015-0090-9.].

Gut resistome development in healthy twin pairs in the first year of life.

BACKGROUND: The early life of the human host marks a critically important time for establishment of the gut microbial community, yet the developmental trajectory of gut community-encoded resistance genes (resistome) is unknown. We present a longitudinal study of the fecal antibiotic resistome of healthy amoxicillin-exposed and antibiotic-naive twins and their mothers during the first year of life. RESULTS: We extracted metagenomic DNA (mgDNA) from fecal samples collected from three healthy twin pairs at three timepoints (1 or 2 months, 6 or 7 months, and 11 months) and from their mothers (collected at delivery). The mgDNA was used to construct metagenomic expression libraries in an Escherichia coli host. These libraries were screened for antibiotic resistance, and functionally selected resistance genes were sequenced and annotated. A diverse fecal resistome distinct from the maternal resistome was apparent by 2 months of age, and infants' fecal resistomes included resistance to clinically important broad-spectrum beta-lactam antibiotics (e.g., piperacillin-tazobactam, aztreonam, cefepime) not found in their mothers. Dissemination of resistance genes among members of a given family was positively correlated with sharing of those same resistance genes between unrelated families, potentially identifying within-family sharing as a marker of resistance genes emerging in the human community at large. Finally, we found a distinct developmental trajectory for a community-encoded function: chloramphenicol resistance. All study subjects at all timepoints harbored chloramphenicol resistance determinants, but multidrug efflux pumps (rarely found in mothers) were the primary effectors of chloramphenicol resistance in young infants. Chloramphenicol acetyltransferases were more common in mothers than in infants and were found in nearly all the infants at later timepoints. CONCLUSIONS: Our results suggest that healthy 1-2-month-old infants' gut microbes harbor clinically relevant resistance genes distinct from those of their mothers, and that family-specific shared environmental factors early in life shape resistome development.

Neural synchrony examined with magnetoencephalography (MEG) during eye gaze processing in autism spectrum disorders: preliminary findings.

BACKGROUND: Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. METHODS: This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M Age = 16.6) compared to neurotypicals (NT) (M Age = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), and low gamma (30 to 45 Hz)) was calculated. RESULTS: Significantly higher coherence and synchronization in posterior brain regions (temporo-parietal-occipital) across all frequencies was evident in ASD, particularly within the low 0 to 15 Hz frequency range. Higher coherence in fronto-temporo-parietal regions was noted in NT. A significantly higher number of low frequency cross-hemispheric synchronous connections and a near absence of right intra-hemispheric coherence in the beta frequency band were noted in ASD. Significantly higher low frequency coherent activity in bilateral temporo-parieto-occipital cortical regions and higher gamma band coherence in right temporo-parieto-occipital brain regions during averted gaze was related to more severe symptomology as reported on the Autism Diagnostic Interview-Revised (ADI-R). CONCLUSIONS: The preliminary results suggest a pattern of aberrant connectivity that includes higher low frequency synchronization in posterior cortical regions, lack of long-range right hemispheric beta and gamma coherence, and decreased coherence in fronto-temporo-parietal regions necessary for orienting to shifts in eye gaze in ASD; a critical behavior essential for social communication.

Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes.

Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation.

Functional metagenomic investigations of the human intestinal microbiota.

The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host.

A prospective study of posttraumatic growth as assessed by self-report and family caregiver in the context of advanced cancer.

OBJECTIVE: The study of posttraumatic growth (PTG) has burgeoned over the last decade, particularly in the area of oncology. The aims of the study were to: (1) describe PTG in patients with hepatobiliary carcinoma, (2) examine agreement between the patient and caregiver measures of patient PTG, and (3) test the associations between PTG and other psychological factors and clinically relevant outcomes. METHODS: Two hundred and two patients with hepatobiliary carcinoma completed a battery of standardized questionnaires that measured PTG, depressive symptoms, optimism, expressed emotion, and quality of life (QOL). A subsample of family caregivers also completed ratings of patient PTG, using the Posttraumatic Growth Inventory (PTGI), as well as their own PTG. RESULTS: No significant increase in the patients' PTG was observed between diagnosis and 6-month follow-up with the exception of the Relating to Others subscale of the PTGI. PTG was not found to be associated with QOL or depressive symptoms. At diagnosis, the agreement between the patients' PTG and family caregivers' rating of patient PTG was found to be high (ICC=0.34-0.74, p=0.001-0.05). PTG was found to be significantly associated with optimism (r=0.20 p=0.02-0.05) and traumatic life events reported in the past 3 years, including recent losses (F(1, 52)=6.0, p=0.02) and severe physical injury (F(1, 52)=5.5, p=0.02). Caregivers reported PTG as a result of their loved one's diagnosis of cancer. CONCLUSION: Preliminary results suggest that PTG is relatively stable over the first 6 months after diagnosis and changes as a result of a diagnosis of cancer were reported, and possibly observed, by others. Family caregivers also experience PTG as a result of their loved one's diagnosis of advanced cancer.