Role of gut microbiota in aging-related health decline: insights from invertebrate models

Studies in mammals, including humans, have reported age-related changes in microbiota dynamics. A major challenge, however, is to dissect the cause and effect relationships involved. Invertebrate model organisms such as the fruit fly Drosophila and the nematode Caenorhabditis elegans have been invaluable in studies of the biological mechanisms of aging. Indeed, studies in flies and worms have resulted in the identification of a number of interventions that can slow aging and prolong life span. In this review, we discuss recent work using invertebrate models to provide insight into the interplay between microbiota dynamics, intestinal homeostasis during aging and life span determination. An emerging theme from these studies is that the microbiota contributes to cellular and physiological changes in the aging intestine and, in some cases, age-related shifts in microbiota dynamics can drive health decline in aged animals.     

Structures of maridomycin I,III, IV,V and VI,macrolide antibiotics

Zusammenfassung Strukturaufklärung einer Gruppe von Antibiotika aus der Reihe der Makrolide.     

New antibiotics,trichopolyns A and B: Isolation and biological activity

Summary Polypeptide antibiotics, trichopolyns A and B, were isolated from the culture broth ofTrichoderma polysporum (Link ex Pers) Rifai (TMI 60146). Assessment of biological activity of the antibiotics against microorganisms was made.Acknowledgment. We are most grateful to Central Research Division, Takeda Chemical Industry Co. Limited, for determination of antifungal and antibacterial spectra.     

The monamycins,a new family of cyclodepsipeptide antibiotics

Zusammenfassung Die Analyse von Monamycin, einem Antibiotika-Komplex, führte zur Identifizierung der 15 Cyclohexadepsipeptidkomponenten. Für Monamycin D₁ wurde Strukturformel V abgeleitet.     

Prianicin A and B,nor-sesterterpenoid peroxide antibiotics from red sea sponges

Summary The antibiotic properties of 2 acidic C₂₄H₄₀O₄ nor-sesterterpenoid peroxides, prianicin A (1) and B (2), against gram-positive and gram-negative bacteria, and against fungi are herein described. They are 4–10 times more effective than tetracycline againstbeta hemolytic Streptococcus, but significantly non-effective against a variety of gram-negative bacteria.Acknowledgment. The authors are grateful to Prof. A. Kjaer of the Organic Chemistry Department of the Technical University of Denmark, for his help and fruitful discussions.     

Selected aspects of the human gut microbiota

The gut microbiota represents a highly complex assembly of microbes, which interact with each other and with their host. These interactions have various implications in terms of health and disease, and this multi-author review issue will address a number of selected aspects pertaining to gut microbiota research.     

Implication of gut microbiota metabolites in cardiovascular and metabolic diseases

Evidence from the literature keeps highlighting the impact of mutualistic bacterial communities of the gut microbiota on human health. The gut microbita is a complex ecosystem of symbiotic bacteria which contributes to mammalian host biology by processing, otherwise, indigestible nutrients, supplying essential metabolites, and contributing to modulate its immune system. Advances in sequencing technologies have enabled structural analysis of the human gut microbiota and allowed detection of changes in gut bacterial composition in several common diseases, including cardiometabolic disorders. Biological signals sent by the gut microbiota to the host, including microbial metabolites and pro-inflammatory molecules, mediate microbiome–host genome cross-talk. This rapidly expanding line of research can identify disease-causing and disease-predictive microbial metabolite biomarkers, which can be translated into novel biodiagnostic tests, dietary supplements, and nutritional interventions for personalized therapeutic developments in common diseases. Here, we review results from the most significant studies dealing with the association of products from the gut microbial metabolism with cardiometabolic disorders. We underline the importance of these postbiotic biomarkers in the diagnosis and treatment of human disorders.     

The effect of two new peptide antibiotics,the hypelcins,on mitochondrial function

Summary The action on mitochondria of 3 peptide antibiotics, hypelcin-A, hypelcin-B, and alamethicin, was examined. The results showed that they are unique uncouplers of oxidative phosphorylation, with the same mechanism of action.     

Interaction of polyene antibiotics and serum lipoproteins

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Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A

The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclarcinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quandriradial chromosomal exchange fiqures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.     

Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A

Summary The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclacinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quadriradial chromosomal exchange figures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.     

Bacterial targets and antibiotics: genome-based drug discovery

The requirement for novel classes of antibiotics to combat the emergence of resistant and multi-resistant bacteria has coincided with the completion sequencing of a number of bacterial genomes. The in silico analysis of these genomes coupled with innovative genetic manipulation has already led to the identification of conserved essential (either in vitro or in vivo, depending on the methodology) genes that are potential targets for antibacterial research. New technologies, made possible by access to the genomic sequences, are capable of simultaneously quantifying almost the entire complement of gene products synthesised by bacterial cells. These technologies are opening up the way for the analysis of expression patterns elicited in cells in response to changes in their environment. The integration of these technologies into the drug discovery process is still in its infancy and the potential wealth of information, some of it already available, has yet to be fully realised.     

Aminoglycoside antibiotics: old drugs and new therapeutic approaches

Aminoglycoside antibiotics kill bacteria by binding to the ribosomal decoding site and reducing fidelity of protein synthesis. Since the discovery of these natural products over 50 years ago, aminoglycosides have provided a mainstay of antibacterial therapy of serious Gram-negative infections. In recent years, aminoglycosides have become important tools to study molecular recognition of ribonucleic acid (RNA). In an ingenious exploitation of the aminoglycosides’ mechanism of action, it has been speculated that drug-induced readthrough of premature stop codons in mutated messenger RNAs might be used to treat patients suffering from certain heritable genetic disorders. Received 23 January 2007; received after revision 25 February 2007; accepted 29 March 2007