Revealing the Bacterial Butyrate Synthesis Pathways by Analyzing (Meta)genomic Data
By M. Vital, A. Howe, James M. Tiedje. mBio, 2014
1,026 citations recorded by the source corpus.
ABSTRACT Butyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by 16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within the Firmicutes, but members of nine other phyla, especially from Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae, were also identified as potential butyrate producers. The established gene catalogue (3,055 entries) was used to screen for butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the acetyl-coenzyme A (CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the lysine pathway (mean, 11.2%). Diversity analysis for the acetyl-CoA pathway showed that the same few firmicute groups associated with several Lachnospiraceae and Ruminococcaceae were dominating in most individuals, whereas the other pathways were associated primarily with Bacteroidetes. IMPORTANCE Microbiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the butyrate-producing potential of complex microbial communities from “-omics”-derived data. Furthermore, a reference data set containing the abundance and diversity of butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of butyrate producers in health and disease and may assist the development of treatments for functional dysbiosis. Microbiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the butyrate-producing potential of complex microbial communities from “-omics”-derived data. Furthermore, a reference data set containing the abundance and diversity of butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of butyrate producers in health and disease and may assist the development of treatments for functional dysbiosis.
Subfields: Food Science, Molecular Biology, Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/50b8cab3fcc7487408883ef753da86029a908c32
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Citations in the corpus
- Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases (2019, background): “Still, the list of butyrate-producing bacteria may be much longer as members of Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae are potential butyrate producers according to the genes they express, including those that encode enzymes that synthesize butyrat”
- The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “, 2004b), there are three alternative synthesis pathways described, starting from glutarate, lysine, and succinate, which converge on the intermediate product crotonyl-CoA (Vital et al., 2014) (Fig.”
- From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. (2016, positive): “Analysis of metagenome data also suggested that butyrate can be synthesized from proteins via the lysine pathway (Vital et al., 2014), further suggesting that microbes in the gut can adapt to nutritional switches in order to maintain the synthesis of essential metabolites such as SCFAs.”
- Microbiota-activated PPAR-γ-signaling inhibits dysbiotic Enterobacteriaceae expansion (2017, neutral): “1C and S3B), which are obligate anaerobes that include abundant butyrate-producers (9) (Fig.”
- Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella (2016, background): “Clostridia are the main producers of butyrate (Louis and Flint, 2009; Vital et al., 2014), which serves as the preferred energy source for colonocytes (enterocytes of the colon).”
- Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics (2016, methodology): “We present simulations to assess the number of sequences that are required to perform reliable appraisals of bacterial community structure.”
- Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota (2023, background): “While most butyrate-producing microbes are classified under the Firmicutes phylum, research has indicated that some species from Actinobacteria, Fusobacteria or even Proteobacteria can also generate butyrate [106,107].”
- Formation of propionate and butyrate by the human colonic microbiota. (2017, background): “However, there is genomic and metagenomic evidence that they are also present in some gut bacteria (Potrykus et al., 2008; Vital et al., 2014).”
- Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut (2016, background): “Only a few butyrate-producing colon bacteria, encompassing Clostridium butyricum, Coprococcus eutactus, and Coprococcus comes, are known to use a butyrate kinase to produce butyrate (Louis and Flint, 2009; Vital et al., 2014).”
- A comparative and functional genomics analysis of the genus Romboutsia provides insight into adaptation to an intestinal lifestyle (2019, background): “The 371 pathways are co-located in the genome, suggesting that the acetoacetyl-CoA formed during lysine 372 fermentation can be directly used as substrate in the acetyl-CoA pathway for additional energy 373 conservation (56, 57).”
- Gut microbiota functions: metabolism of nutrients and other food components (2017, background): “Metagenomic screening of more than 3000 sequenced bacterial genomes identified many other species containing butyrate production pathways, with no consistency within families [19].”
- Enhanced volatile fatty acids production from anaerobic fermentation of food waste: A mini-review focusing on acidogenic metabolic pathways. (2018, neutral): “The final step from butyryl-CoA to butyrate is either catalyzed by enzymes phosphotransbutyrylase and butyrate-kinase or catalyzed by the butyryl-CoA: acetate CoA-transferase (Vital et al., 2014).”