Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an AMzelmer-like dementia. Moreover, DS is a model for the study of human aneuploldy. Although With the discovery that DS was caused by trisomy 21 (3, 4), and the subsequent proposal that chromosome 21 band q22 was "pathogenetic" for DS (5), the foundation was laid for elucidating the fundamental biochemical and morphogenetic pathways of abnormal development in this aneuploidy. There followed a series ofreports ofindividuals with "partial trisomy 21" (for review, see ref. 6) that appeared to indicate that regions might be defined that were likely to contain genes responsible for particular features of DS. These studies provide the basis for construction of a DS phenotypic map.By "phenotype" we mean a measurable parameter and include clinical, physical, cellular, and physiological components. By "phenotypic mapping" we mean the molecular definition of a physical region that is likely to contain the gene(s) whose overexpression is ultimately responsible in part for the phenotype. The current revolution in human molecular genetics and the development of a physical map of chromosome 21 now provide the possibility to understand the genetic basis for some of these defects and, therefore, to provide a necessary first step for their prevention, amelioration, and perhaps ultimately, their treatment.Phenotypic maps provide the basis for clinical prognosis for individuals with partial aneuploidy for chromosome 21, and when of high resolution, the basis for the identification of the genes responsible for the phenotypes. One approach to this combines the phenotypic information from individuals with "partial trisomy" such as those described above with a molecular definition of their duplicated chromosomal regions. Once the molecular markers for a region are defined, the genes within it may then be identified, characterized, and ultimately tested for their relationship to a given phenotype. This report describes the molecular and phenotypic definition of these individuals, provides a theoretical framework, and utilizes this to construct a molecular "map" of the phenotypes associated with DS.

ObjectiveAntibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy.MethodsThe total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated.ResultsApparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation.ConclusionsThis proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.

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