![]() ![]() Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut “microbiome” on mammalian blood metabolites. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas ≈10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metabolism. The human body is colonized by hundreds of trillions of microbes, which collectively possess hundreds of times as many genes as coded in the human genome. The combined genetic potential of the endogenous flora is referred to as the “microbiome” ( 1), and typically results in a mutualistic relationship between microbe and host. Normal host activities, including the processing of nutrients and the regulation of the immune system, are affected by the intestinal microbiome ( 2, 3), and the microbiome has been implicated in the pathogenesis of diseases such as nonalcoholic steatohepatitis ( 4), allergy ( 5), the formation of gallstones ( 6), and inflammatory bowel disease ( 7, 8). The composition of the gut microbiome is highly variable ( 9), and its diversity can be significantly affected by alterations in diet ( 2, 10) or antibiotic use ( 11). Alternatively, probiotic therapy is the attempt to alter the extant gut microbial environment through the ingestion of live consumable cultures of beneficial bacteria ( 12). Differences in commensal microflora are likely to impact human health and disease through any number of ways reflective of the complex nature of the microbiome itself. Historically, classical microbiology methods including the isolation and culture of individual bacterial species associated with the gut were used to study microbial colonization of higher organisms. More recently, metagenomic techniques have been used to characterize both the composition and the potential physiological effects of entire microbial communities without having to culture individual community members. ![]() Miscellaneous under-the-hood improvements.For example, genes for specific metabolic pathways such as amino acid and glycan metabolism were found to be overrepresented in the microbiome of the distal gut, reinforcing the notion that human metabolism is an amalgamation of microbial and human attributes ( 13). ![]() What's New in Version 3.2.1 - Added support for iPhone X. Download it today and start your journey! Human Japanese will impress you with its warmth, beauty, and wit. * Dozens of photos and cultural notes to connect your Japanese to real life ![]() * Interactive games and review quizzes that keep track of your response history to help focus on trouble spots * Ingredients(TM) example sentence breakdowns on every example sentence for total clarity * Over 1800 recordings of vocabulary words and phrases spoken by native speakers * Animations of every hiragana and katakana character * More than 500 pages of interactive content Our goal is to lead you from one “light bulb moment” to the next so that you stay energized and excited about the language. Key concepts are explained with warmth and humor, drawing you into the nuts-and-bolts that you need to understand Japanese while keeping things down-to-earth and engaging. This makes your journey into Japanese a joy, as each new piece that falls into place makes sense and every new example sentence is comprehensible. The core promise of Human Japanese is to show you how everything works and never to expect you to magically know things that we haven’t yet taught you. Going much deeper than the canned phrases and vocab of other products, it approaches the language in an integrated way, with discussion, recordings, animations, illustrations, photos, reviews, and more. Human Japanese presents the Japanese language from square one in a warm, engaging tone. Ready to learn Japanese? Meet your personal sensei-in-a-box. ![]()
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