Draft genome sequence of Treponema sp. strain JC4, a novel spirochete isolated from the bovine rumen

Morphologically and biochemically diverse members of the Treponema genus are present in the gastrointestinal tract of ruminants, yet very little is understood about their functional importance to this microbiome. Here we describe the annotated draft genome sequence of Treponema sp. strain JC4, a novel spirochete isolated from a bovine rumen sample

Diet and the microbiome

The gut microbiota provides a range of ecologic, metabolic, and immunomodulatory functions relevant to health and well-being. The gut microbiota not only responds quickly to changes in diet, but this dynamic equilibrium may be managed to prevent and/or treat acute and chronic diseases. This article provides a working definition of the term “microbiome” and uses two examples of dietary interventions for the treatment of large bowel conditions to emphasize the links between diet and microbiome. There remains a need to develop a better functional understanding of the microbiota, if its management for clinical utility is to be fully realized

Fast forward bioprospecting of the gut microbiota for novel live biotherapeutics and anti-inflammatory bioactives

Microba has identified over 800 numerically abundant and prevalent gut bacteria associated with human health, which are underrepresented or absent in several disease states including inflammatory bowel disease (IBD), asthma, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), hypertension, anxiety and depression. These comprise a heterogenous group of diseases however several feature inflammation as a major pathology. Notably, the nuclear factor‐κB (NF‐κB) driven inflammatory response plays a central role in the pathogenesis of IBD, asthma and GERD, and it also plays a role in other diseases including metabolic disease, colorectal cancer (CRC), rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disorder (COPD) and atherosclerosis. Inflammation is the primary pathology in IBD and Microba researchers have demonstrated gut bacteria produce potent NF‐κB suppressive bioactives. Moreover, we have established methodologies relevant to IBD that could expedite the identification of precision Live Biotherapeutics (LBPs) and NF‐κB suppressive bioactives. These LBPs and/or their bioactives could potentially be exploited to prevent or treat IBD

Fast forward bioprospecting of the gut microbiota for novel live biotherapeutics and anti-inflammatory bioactives

Microba has identified over 800 numerically abundant and prevalent gut bacteria associated with human health, which are underrepresented or absent in several disease states including inflammatory bowel disease (IBD), asthma, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), hypertension, anxiety and depression. These comprise a heterogenous group of diseases however several feature inflammation as a major pathology. Notably, the nuclear factor‐κB (NF‐κB) driven inflammatory response plays a central role in the pathogenesis of IBD, asthma and GERD, and it also plays a role in other diseases including metabolic disease, colorectal cancer (CRC), rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disorder (COPD) and atherosclerosis. Inflammation is the primary pathology in IBD and Microba researchers have demonstrated gut bacteria produce potent NF‐κB suppressive bioactives. Moreover, we have established methodologies relevant to IBD that could expedite the identification of precision Live Biotherapeutics (LBPs) and NF‐κB suppressive bioactives. These LBPs and/or their bioactives could potentially be exploited to prevent or treat IBD

Colonic thioguanine pro-drug: investigation of microbiome and novel host metabolism

Thiopurines are analogues of endogenous purines. They are pro-drugs which require the purine salvage pathway to convert them to the active drug nucleotides (TGN). These drugs are used to maintain clinical remission in patients with inflammatory bowel diseases. In our recent Gut paper, we showed that thioguanine worked quickly to improve colitis in the absence in the host animal of the key guanine salvage enzyme, hypoxanthine-guanine-phosphoribosyltransferase (HPRT). Current evidence favours the proposition that active drug delivery to the host lacking HPRT requires translocation of TGN-loaded bacteria across the inflamed mucosal barrier, and most likely delivery by phagocytosis. Alternatively, the efficacy of thioguanine in treating colitis could be mediated by modulation of the community of the microbiota in the intestine, or there are novel host pathways for conversion of the thioguanine pro-drug to TGN

Isolation of genetically tractable most-wanted bacteria by metaparental mating

Metagenomics has rapidly advanced our inventory and appreciation of the genetic potential inherent to the gut microbiome. However it is widely accepted that two key constraints to further genetic dissection of the gut microbiota and host-microbe interactions have been our inability to recover new isolates from the human gut, and the paucity of genetically tractable gut microbes. To address this challenge we developed a modular RP4 mobilisable recombinant vector system and an approach termed metaparental mating to support the rapid and directed isolation of genetically tractable fastidious gut bacteria. Using this approach we isolated transconjugants affiliated with Clostridium cluster IV (Faecalibacterium and Oscillibacter spp.), Clostridium cluster XI (Anaerococcus) and Clostridium XIVa (Blautia spp.) and group 2 ruminococci amongst others, and demonstrated that the recombinant vectors were stably maintained in their recipient hosts. By a similar approach we constructed fluorescently labelled bacterial transconjugants affiliated with Clostridium cluster IV (including Flavonifractor and Pseudoflavonifractor spp.), Clostridium XIVa (Blautia spp.) and Clostridium cluster XVIII (Clostridium ramosum) that expressed a flavin mononucleotide-based reporter gene (evoglow-C-Bs2). Our approach will advance the integration of bacterial genetics with metagenomics and realize new directions to support a more mechanistic dissection of host-microbe associations relevant to human health and disease