Liquid Chromatography-tandem mass spectrometry-based metabolite profiling in the hearts of germ-free and conventionally-raised mice

The microbiota is the community of microorganisms living on and in a biological system. It has shown to play a role in a broad range of medical conditions, including cardiovascular diseases. Germ-free (GF) mice grew under the condition lacking all microorganisms, in contrast to conventionally raised (CONV-R) mice colonized with a diverse microbiota. GF mice play a key role as tools to reveal the the causal relationship between microbiome and disease. In particular, GF mice present significant cardiac functional defects compared to CONV-R mice. The project's goal was to determine the spatial impact of GF vs. CONV-R status on cardiac metabolism across cardiac regions. 4 metabolite molecules showed significant differences by Random Forest analysis based on untargeted liquid chromatography-tandem mass spectrometry data. The four molecules are neighborhood of ADP-ribose (m/z = 588.11), ergothioneine (m/z = 230.1), neighborhood of dodecanoic acid (m/z = 177.13), and L-glutamine (m/z = 130.05). (Neighborhood results were generated from molecular networking.) Parallel reaction monitoring (PRM) was applied to provide more precise quantification results. In most locations, peak abundance significant difference was mapping in the locations: right ventricle free wall and left atrium part between germ-free and CONV-R conditions. Ergothioneine showed a difference in the left ventricle free wall bottom section. The metabolites may relate to the presence of microbiome and contribute to reducing the risk of cardiovascular disease

Abundancia, nidificación y aprovechamiento de podocnemis unifilis (peta) y P. expansa (tataruga) en el río Blanco (cuenca del río Iténez, Amazonía boliviana)

Las poblaciones de las tortugas de agua dulce Podocnemis unifilis y P. expansa han sido poco estudiadas en Bolivia. El objetivo del presente trabajo es de presentar una línea base sobre la presencia de ambas especies en un tributario del río Iténez (río Blanco) y sobre su aprovechamiento por dos comunidades locales. Se realizaron avistamientos de P. unifilis a lo largo de un transecto de 100 km, además se realizaron observaciones sobre los patrones de nidificación de ambas especies. La carne y los huevos de ambas especies son importantes fuentes alimenticias para las poblaciones humanas locales. Se recomienda la implementación de estrategias de manejo sostenible de las poblaciones de las tortugas en la cuenca del río Iténez.As populações de tartarugas de água doce Podocnemis unifilis e P. expansa tem sido pouco estudadas na Bolivia. O objetivo deste trabalho é apresentar um marco sobre a presença de ambas as espécies em um afluente do rio Guaporé* (rio Blanco) e seu uso por duas comunidades locais. Avistamentos de P. unifilis foram realizados ao longo de um transecto de 100 km, bem como observações foram feitas sobre os padrões de nidificação de ambas as espécies. A carne e os ovos de ambas as espécies sao fontes de alimento importantes para populações humanas locais. Recomenda-se a implementação de estratégias para o manejo sustentável das populações de tartarugas na bacia do rio Guaporé.* Iténez e denominado rio Guaporé no Brasil.The populations of the freshwater turtles Podocnemis unifilis and P. expansa have been little studied in Bolivia. The aim of this paper is to present a baseline on the presence of both species in a tributary of the Iténez* river (Blanco river) and its use by two local communities. Sightings were made of P. unifilis along a transect of 100 km; observations were also made on the nesting pattems of both species. Meat and eggs of both species are important food sources for local human populations. The implementation of sustainable management strategies for populations of turtles in the Iténez river basin is recommended.* The Iténez river is known as Guaporé river in Brasil

Gut microbiome variation modulates the effects of dietary fiber on host metabolism

Background: There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. Results: We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional, and metabolomic analyses revealed diet-directed differences between animals colonized with the two communities, including variation in amino acids and lipid pathways that were associated with divergent health outcomes. Conclusion: This study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approach to promote health is unlikely to elicit consistent effects across individuals. Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy. [MediaObject not available: see fulltext.]Fil: Murga Garrido, Sofia M.. Universidad Nacional Autónoma de México; México. University of Wisconsin; Estados UnidosFil: Hong, Qilin. University of Wisconsin; Estados UnidosFil: Cross, Tzu Wen L.. University of Wisconsin; Estados Unidos. Purdue University; Estados UnidosFil: Hutchison, Evan R.. University of Wisconsin; Estados UnidosFil: Han, Jessica. Wisconsin Institute for Discovery; Estados UnidosFil: Thomas, Sydney P.. Wisconsin Institute for Discovery; Estados UnidosFil: Vivas, Eugenio I.. University of Wisconsin; Estados UnidosFil: Denu, John. Wisconsin Institute for Discovery; Estados UnidosFil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Tang, Zheng Zheng. University of Wisconsin; Estados Unidos. Wisconsin Institute for Discovery; Estados UnidosFil: Rey, Federico E.. University of Wisconsin; Estados Unido

Bacteroides thetaiotaomicron Starch Utilization Promotes Quercetin Degradation and Butyrate Production by Eubacterium ramulus

Consumption of flavonoids has been associated with protection against cardiovascular and neurodegenerative diseases. Most dietary flavonoids are subjected to bacterial transformations in the gut where they are converted into biologically active metabolites that are more bioavailable and have distinct effects relative to the parent compounds. While some of the pathways involved in the breakdown of flavonoids are emerging, little it is known about the impact of carbon source availability and community dynamics on flavonoid metabolism. This is relevant in the gut where there is a fierce competition for nutrients. In this study, we show that metabolism of one of the most commonly consumed flavonoids, quercetin, by the gut-associated bacterium Eubacterium ramulus is dependent on interspecies cross-feeding interactions when starch is the only energy source available. E. ramulus can degrade quercetin in the presence of glucose but is unable to use starch for growth or quercetin degradation. However, the starch-metabolizing bacterium Bacteroides thetaiotaomicron, which does not metabolize quercetin, stimulates degradation of quercetin and butyrate production by E. ramulus via cross-feeding of glucose and maltose molecules released from starch. These results suggest that dietary substrates and interactions between species modulate the degradation of flavonoids and production of butyrate, thus shaping their bioavailability and bioactivity, and likely impacting their health-promoting effects in humans

Genetic determinants of gut microbiota composition and bile acid profiles in mice.

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions

Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut.

The molecular bases of how host genetic variation impacts the gut microbiome remain largely unknown. Here we used a genetically diverse mouse population and applied systems genetics strategies to identify interactions between host and microbe phenotypes including microbial functions, using faecal metagenomics, small intestinal transcripts and caecal lipids that influence microbe-host dynamics. Quantitative trait locus (QTL) mapping identified murine genomic regions associated with variations in bacterial taxa; bacterial functions including motility, sporulation and lipopolysaccharide production and levels of bacterial- and host-derived lipids. We found overlapping QTL for the abundance of Akkermansia muciniphila and caecal levels of ornithine lipids. Follow-up in vitro and in vivo studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that ornithine lipids have immunomodulatory effects and identified intestinal transcripts co-regulated with these traits including Atf3, which encodes for a transcription factor that plays vital roles in modulating metabolism and immunity. Collectively, these results suggest that ornithine lipids are potentially important for A. muciniphila-host interactions and support the role of host genetics as a determinant of responses to gut microbes

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks