In recent years, short-chain fatty acids (SCFAs) have been reported to play an important role in maintaining human health. Fecal SCFA concentrations correlate well with colonic SCFA status and gut microbiota composition. However, the associations with the gut microbiota functional pathway, dietary intake, blood SCFAs, and fecal SCFAs remain uncertain. To clarify these relationships, we collected fecal samples, blood samples, and dietary habit data from 12 healthy adults aged 22-51 years. The relative abundance of several SCFA-producing bacteria, gut microbiota diversity, and functional pathways related to SCFA biosynthesis were positively associated with fecal SCFAs even after adjusting for age and sex. Furthermore, fecal acetate was likely to be positively associated with serum acetate. By contrast, dietary intake was not associated with fecal SCFAs. Overall, the present study highlights the potential usefulness of fecal SCFAs as an indicator of the gut microbiota ecosystem and dynamics of SCFAs in the human body.
The use of polyunsaturated fatty acids (PUFA) as medicine or in functional diets requires high purity. An industrial purification method for PUFA from Schizochytrium sp. SR21 oil was investigated. This oil contains fewer unwanted components than fish oils. Docosahexaenoic acid and docosapentaenoic acid ethyl esters (DHA-E and DPA-E) were prepared by treatment of this oil with ethanol and 1 N potassium hydroxide in hexane. DHA-E and DPA-E were purified by an industrial high-performance liquid chromatography (HPLC) plant. The separation plant consists of two columns (400 mm i.d., 1,000 mmL) with temperature-controlled water jackets and double-plunger (four heads) injection and eluent pumps. This plant was computer-controlled and equipped with an explosion-prevention system. The packed material was octadecylsilica (reverse-phase ODS), and the eluent was methyl alcohol/water (98:2). DHA-E and DPA-E from single-cell oil were highly purified by this industrial HPLC method in a onestep process. The DHA-E and DPA-E obtained were better than 99% purity. JAOCS 74, 1435-1440 (1997).KEY WORDS: DHA, docosahexaenoic acid ester, n-6 docosapentaenoic acid ester, DPA, preparative high-performance liquid chromatography, single-cell oil.
Gut microbiota has been reported to be closely related to host energy metabolism and immunity, and thus influence the development and progression of various human diseases. To date, the gut microbial metabolites such as short-chain fatty acids, defensins, cathelicidins, and lactoferrin in feces have been investigated as biomarkers associated with various disease conditions. In this review, we introduce intestinal and fecal pH, which is relatively easy and rapid to measure compared to the composition of the gut microbiota and its metabolites. In particular, this review presents the distribution of pH in the human body, its role and clinical significance, and various factors that affect intestinal and fecal pH, including the gut microbiota and its metabolites.
Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the genetic signature in PDAC (KRAS, TP53, CDKN2A, and SMAD4 alterations), which is associated with the worst prognosis in patients. The ‘4-hit’ flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK inhibitor trametinib and the AURKB inhibitor BI-831266 suppressed the growth of human PDAC xenografts in mice. In patients with PDAC, the activity of AURKB was associated with poor prognosis. This fly-based platform provides an efficient whole-body approach that complements current methods for identifying therapeutic targets in PDAC.
Significance:
Development of a Drosophila model mimicking genetic alterations in human pancreatic ductal adenocarcinoma provides a tool for genetic screening that identifies MEK and AURKB inhibition as a potential treatment strategy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.