Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

Symbiotic bacteria often help their hosts acquire nutrients from their diet, showing trends of coevolution and independent acquisition by hosts from the same trophic levels. While these trends hint at important roles for biotic factors, the effects of the abiotic environment on symbiotic community composition remain comparably understudied. In this investigation, we examined the influence of abiotic and biotic factors on the gut bacterial communities of fish from different taxa, trophic levels and habitats. Phylogenetic and statistical analyses of 25 16S rRNA libraries revealed that salinity, trophic level and possibly host phylogeny shape the composition of fish gut bacteria. When analysed alongside bacterial communities from other environments, fish gut communities typically clustered with gut communities from mammals and insects. Similar consideration of individual phylotypes (vs. communities) revealed evolutionary ties between fish gut microbes and symbionts of animals, as many of the bacteria from the guts of herbivorous fish were closely related to those from mammals. Our results indicate that fish harbour more specialized gut communities than previously recognized. They also highlight a trend of convergent acquisition of similar bacterial communities by fish and mammals, raising the possibility that fish were the first to evolve symbioses resembling those found among extant gut fermenting mammals. Data accessibility DNA sequences of Poecilia reticulata gut bacteria: GenBank accession numbers JQ253406-JQ253517. Additional information regarding the metadata included in this paper is available in Tables S1 and S2 (Supporting information). Supporting informationAdditional supporting information may be found in the online version of this article. Table S1 Habitats, lifestyles, and phylogenetic affiliations of fish gut bacteria and their closest GenBank relatives. Table S2 List of primers used in all studies included in this meta-analysis. Fig. S1 Ordinal classifications of sequences from whole libraries of fish that were derived from culture independent methods.

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The role of melatonin as an immunomodulator is well established. Recent reports showed that melatonin exerts protective effects in septic and hemorrhagic shock and in inflammation. The expression of the inducible isoform of nitric oxide synthase (iNOS) makes an important contribution to the pathophysiology of shock and inflammation. We studied, in cultured murine macrophages, the role of melatonin in the regulation of the expression of iNOS and defined the mode of melatonin's action. Our results show that melatonin, at 1 microM-1 mM, decreased the production of nitrite/nitrate (the breakdown products of NO) as well as the production of 6-keto-prostaglandin F1alpha (the major stable breakdown product of prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10 microg/ml). We observed that melatonin reduces iNOS steady-state mRNA levels and iNOS protein expression in the same concentration range (1 microM-1 mM). Melatonin, up to 10 mM, exerted only a slight direct inhibitory effect on iNOS activity. Using iNOS promoter-luciferase constructs, we found that melatonin inhibits iNOS promoter activation. Inhibition of iNOS expression was associated with inhibition of activation of the transcription factor nuclear factor kappa B (NFkappaB). We conclude that melatonin inhibits NO production in immunostimulated macrophages mainly by inhibiting the expression of iNOS. This is due to inhibition of iNOS transcription, in part through inhibition of NFkappaB activation. Inhibition of iNOS-derived NO production by melatonin may contribute to the anti-inflammatory effects of this pineal secretory product.

Summary 1.Life histories evolve as a response to multiple agents of selection, such as age-specific mortality, resource availability or environmental fluctuations. Predators can affect life-history evolution directly, by increasing the mortality of prey, and indirectly, by modifying prey density and resources available to the survivors. Increasing survivor densities can intensify intraspecific competition and cause evolutionary changes in their selectivity, also affecting nutrient acquisition. 2. Here, we show that different life-history traits in guppies (Poecilia reticulata) are correlated with differences in resource consumption and prey selectivity. We examined differences in wildcaught guppy diet among stream types with high (HP) and low predation (LP) pressure and how they are related to benthic invertebrate biomass. Fish and invertebrate samples were collected from two HP and two LP reaches of two distinct study rivers in Trinidad. 3. Our results reveal a strong association between life history and diet. Guppies from HP environments mature earlier and have higher fecundity and reproductive allotment than those from LP environments. Prior work revealed that their population densities are lower and that they grow faster than their LP counterparts. Here, we show that these life-history differences are repeated and that HP guppies feed primarily on invertebrates. In contrast, guppies from LP sites feed primarily on detritus and algae, which are a poorer quality food. LP guppies fed on invertebrates according to their availability, while HP guppies were selective towards those invertebrates with the lower carbon ⁄ nitrogen body ratio and thus with higher nutritional value. 4. Our study suggests that as predators shape the life histories of their prey and alter prey population densities, they can also indirectly shape their prey's foraging and diet selectivity. This is, to our knowledge, the first report on how intraspecific differences in life-history traits are correlated with prey selectivity, where prey stoichiometry is included. Although there are clear limitations of association data, our study suggests that the patterns of resource use and life history evolve in concert with one another. However, further research is needed to investigate the possible causal links between risk of predation, the indirect effects of predators on guppy population density, the evolution of life-history traits and nutrient acquisition.

Peroxynitrite, a cytotoxic oxidant formed from nitric oxide (NO) and superoxide, induces DNA strand breakage, which activates the nuclear enzyme poly(ADPribose) synthase (PARS; EC 2.4.2.30). The cellular function of PARS was determined in fibroblast lines from PARS knockout animals (PARS ؊/؊ ) and corresponding wild-type animals (PARS ؉/؉ ), with the aid of the lipophilic PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH 2 BP). We investigated the role of PARS in peroxynitrite-induced fibroblast injury in vitro and also in the development of arthritis in vivo. Nitric oxide (NO), superoxide, and their cytotoxic reaction product peroxynitrite (ONOO Ϫ ) are terminal mediators of cellular injury in various forms of inflammation. In vitro studies employing conventional inhibitors of the nuclear enzyme poly(ADP-ribose) synthase (PARS; EC 2.4.2.30) suggested that the oxidative injury in response to oxy radicals and peroxynitrite is related to DNA single-strand breakage and consequent activation of PARS (1, 2). Massive ADPribosylation of nuclear proteins by PARS then results in cellular energy depletion and injury, reminiscent of necrosis (1-3). However, objections can be raised against the conclusions of these studies, because the commonly used relatively high concentrations of PARS inhibitors (e.g., nicotinamide and benzamide analogs), have additional effects as free radical scavengers, and have short cellular residence time (4-6).More recently a potent pharmacologically active inhibitor of PARS, the lipophilic 6-iodo-5-amino-1,2-benzopyrone (INH 2 BP), was developed (7, 8). Moreover, a genetically engineered mouse line that lacks PARS is now available: a fibroblast cell line from these animals can be used for in vitro investigations (9). These tools allow a direct testing of the role of PARS. The present work was designed to elucidate (i) whether inhibition of PARS by INH 2 BP protects against cellular oxidant injury triggered by peroxynitrite, a cytotoxic oxidant produced by the reaction of superoxide and NO (10-14); (ii) whether the PARS The results of the current study support the role of PARS activation in the peroxynitrite-mediated cellular oxidant injury and inflammation, and they demonstrate that either deletion of PARS or its selective inhibition by INH 2 BP protects against inflammatory cell injury.