Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic

ABSTRACT Antibiotics are a mainstay of modern medicine, but as they kill their target pathogen(s), they often affect the commensal microbiota. Antibiotic-induced microbiome dysbiosis is a growing research focus and health concern, often assessed via analysis of fecal samples. However, such analysis does not inform how antibiotics influence the microbiome across the whole host or how such changes subsequently alter host chemistry. In this study, we investigated the acute (1 day postadministration) and delayed (6 days postadministration) effects of a single parenteral dose of two common antibiotics, ampicillin or vancomycin, on the global metabolome and microbiome of mice across 77 different body sites from 25 different organs. The broader-spectrum agent ampicillin had the greatest impact on the microbiota in the lower gastrointestinal tract (cecum and colon), where microbial diversity is highest. In the metabolome, the greatest effects were seen 1 day posttreatment, and changes in metabolite abundances were not confined to the gut. The local abundance of ampicillin and its metabolites correlated with increased metabolome effect size and a loss of alpha diversity versus control mice. Additionally, small peptides were elevated in the lower gastrointestinal tract of mice 1 day after antibiotic treatment. While a single parenteral dose of antibiotic did not drastically alter the microbiome, nevertheless, changes in the metabolome were observed both within and outside the gut. This study provides a framework for how whole-organism -omics approaches can be employed to understand the impact of antibiotics on the entire host. IMPORTANCE We are just beginning to understand the unintended effects of antibiotics on our microbiomes and health. In this study, we aimed to define an approach by which one could obtain a comprehensive picture of (i) how antibiotics spatiotemporally impact commensal microbes throughout the gut and (ii) how these changes influence host chemistry throughout the body. We found that just a single dose of antibiotic altered host chemistry in a variety of organs and that microbiome alterations were not uniform throughout the gut. As technological advances increase the feasibility of whole-organism studies, we argue that using these approaches can provide further insight on both the wide-ranging effects of antibiotics on health and how to restore microbial communities to mitigate these effects.

Epichloë (formerly Neotyphodium) fungal endophytes increase adaptation of cool-season perennial grasses to environmental stresses

Many cool-season grass species have evolved with asexual, nonsymptomatic fungal endophytes of the genus <em>Epichloë</em> (formerly <em>Neotyphodium</em>) of the family Clavicipitaceae. These associations range from parasitic to mutualistic and have dramatic effects on grass host chemistry, increasing resistance to abiotic (drought, soil mineral imbalance) and biotic (vertebrate and invertebrate herbivory, nematodes, plant pathogens, plant competition) stresses. Native endophyte strains produce a range of bioprotective alkaloid and other nonalkaloid secondary compounds, several of them known to have detrimental effects on grazing animals. In the past two decades, epichloid endophyte strains have been selected with marginal or no capacity of producing ergot and/or lolitrem alkaloids. These novel endophyte strains have been introduced to several grass cultivars with the idea to increase grass host resistance to abiotic stresses without hindering grazing livestock, and abiotic stresses to ensure high competitive ability of symbiotic grass cultivars. In this presentation, we discuss mechanisms underlying the competitiveness of epichloid endophyte/grass associations and consequences of endophyte infection for grassland ecosystem functions.

Enhanced user-control of small molecule drug release from a poly(ethylene glycol) hydrogel via azobenzene/cyclodextrin complex tethers

Photoresponsive azobenzene–cyclodextrin guest–host chemistry can be used to control the release rate of a small peptide from a PEG hydrogel with light.

Determination of Enantiomeric Composition of Dopa by Using UV Spectroscopy Combined with Principal Component Regression

A method which combines UV spectroscopy, guest–host chemistry and principal component regression (PCR) was proposed for determining the enantiomeric composition of DOPA samples. The calibration models were developed from UV spectral data of a series of samples containing DOPA with different known enantiomeric compositions by using PCR. The obtained model was subsequently validated by determining the enantiomeric composition of a set of independently prepared samples. This method shows high sensitivity for determining the enantiomeric composition of DOPA. When there is 5.00 μM DOPA in the samples, the enantiomeric composition of DOPA can be accurately determined.

Self-assembled coordination cage as a molecular flask

Cavity-directed chemical transformations represent one of the most important features in 3-D host chemistry, yet they are unexplored as synthetic receptors. We are developing such functions with the large cavity of self-assembled cages, particularly an M6L4-type cage. The photodimerization of olefins within this cage shows remarkable rate enhancement, perfect regio- and stereoselection, and high pairwise selection (when two different olefins are used) giving only the cross [2+2] adduct. Another intriguing property of the cavity is the stabilization of labile molecules by encapsulation. We succeeded in trapping labile molecules by in situ preparation from small components coming through small portals of the cage. For example, hydrolysis and condensation of PhSi(OMe)3, which ordinarily provides a sophisticated Si-O 3-D network (so-called sol-gel condensation), selectively gave a cyclic trimer, [PhSi(OH)O]3, in a "ship-in-a-bottle" fashion. Cavity-sensitized photochemical oxidation of alkanes within the cage is also discussed.