Showing papers by "Rustam Aminov published in 2011"

Restricting Microbial Exposure in Early Life Negates the Immune Benefits Associated with Gut Colonization in Environments of High Microbial Diversity

Abstract: Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk Although morphological maturation and gut closure were delayed in isolator-reared animals, these hard-wired events occurred later in development Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis

Establishment of normal gut microbiota is compromised under excessive hygiene conditions.

Abstract: Background: Early gut colonization events are purported to have a major impact on the incidence of infectious, inflammatory and autoimmune diseases in later life. Hence, factors which influence this process may have important implications for both human and animal health. Previously, we demonstrated strong influences of early-life environment on gut microbiota composition in adult pigs. Here, we sought to further investigate the impact of limiting microbial exposure during early life on the development of the pig gut microbiota. Methodology/Principal Findings: Outdoor- and indoor-reared animals, exposed to the microbiota in their natural rearing environment for the first two days of life, were transferred to an isolator facility and adult gut microbial diversity was analyzed by 16S rRNA gene sequencing. From a total of 2,196 high-quality 16S rRNA gene sequences, 440 phylotypes were identified in the outdoor group and 431 phylotypes in the indoor group. The majority of clones were assigned to the four phyla Firmicutes (67.5% of all sequences), Proteobacteria (17.7%), Bacteroidetes (13.5%) and to a lesser extent, Actinobacteria (0.1%). Although the initial maternal and environmental microbial inoculum of isolator-reared animals was identical to that of their naturally-reared littermates, the microbial succession and stabilization events reported previously in naturally-reared outdoor animals did not occur. In contrast, the gut microbiota of isolator-reared animals remained highly diverse containing a large number of distinct phylotypes. Conclusions/Significance: The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene.

Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific

Abstract: The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense crosstalk and signalling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF), and in patients with peptic ulceration (PU) resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls) and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified). This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

Antibiotic Resistance in Swine-Manure-Impacted Environments

Abstract: An increasing body of evidence demonstrating entry of antibiotics and antibiotic resistance genes from anthropogenic sources into natural soil and water environments has raised even more questions about the lasting and future impacts consequent to drug resistance development in bacteria. These concerns stem, in part, from emerging knowledge about increased incidences, persistence, and diversity of antibiotic resistance (ABR) genes in soil and water environments with still very limited knowledge about the molecular microbial ecology of ABR occurring in situ in these natural systems. The practice of subtherapeutic doses of antibiotics for use in disease prophylaxis and growth promotion in animal livestock production has been the subject of particularly intense scrutiny, prompting bans of such uses completely in the European Union since 2006 and causing mounting concerns in the United State for more judicious use of antibiotics in food animals. Numerous articles over the last two decades have discussed in detail the various health and environmental aspects concerning the routine use of subtherapeutic antibiotic treatment in animal production (Gustafson and Bowen, 1997; Khachatourians, 1998; USGAO, 1999; Isaacson and Torrence, 2002; Seveno et al., 2002; Kummerer, 2004; Shea, 2004; Chee-Sanford et al., 2009).