Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle.

The rumen is a complex ecosystem composed of anaerobic bacteria, protozoa, fungi, methanogenic archaea and phages These microbes interact closely to breakdown plant material that cannot be digested by humans, whilst providing metabolic energy to the host and, in the case of archaea, producing methane Consequently, ruminants produce meat and milk, which are rich in high-quality protein, vitamins and minerals, and therefore contribute to food security As the world population is predicted to reach approximately 97 billion by 2050, an increase in ruminant production to satisfy global protein demand is necessary, despite limited land availability, and whilst ensuring environmental impact is minimized Although challenging, these goals can be met, but depend on our understanding of the rumen microbiome Attempts to manipulate the rumen microbiome to benefit global agricultural challenges have been ongoing for decades with limited success, mostly due to the lack of a detailed understanding of this microbiome and our limited ability to culture most of these microbes outside the rumen The potential to manipulate the rumen microbiome and meet global livestock challenges through animal breeding and introduction of dietary interventions during early life have recently emerged as promising new technologies Our inability to phenotype ruminants in a high-throughput manner has also hampered progress, although the recent increase in "omic" data may allow further development of mathematical models and rumen microbial gene biomarkers as proxies Advances in computational tools, high-throughput sequencing technologies and cultivation-independent "omics" approaches continue to revolutionize our understanding of the rumen microbiome This will ultimately provide the knowledge framework needed to solve current and future ruminant livestock challenges

/pdf/addressing-global-ruminant-agricultural-challenges-through-3336513qsk.pdf

Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present and future

Antimicrobials for food and feed; a bacteriocin perspective

Staphylococcus aureus (S. aureus) causes persistent biofilm-related infections. Biofilm formation by S. aureus is affected by the culture conditions and is associated with certain genotypic characteristics. Here, we show that glucose and sodium chloride (NaCl) supplementation of culture media, a common practice in studies of biofilms in vitro, influences both biofilm formation by 40 S. aureus clinical isolates (methicillin-resistant and methicillin-sensitive S. aureus) and causes variations in biofilm quantification. Methicillin-resistant strains formed more robust biofilms than methicillin-sensitive strains in tryptic soy broth (TSB). However, glucose supplementation in TSB greatly promoted and stabilized biofilm formation of all strains, while additional NaCl was less efficient in this respect and resulted in significant variation in biofilm measurements. In addition, we observed that the ST239-SCCmec (Staphylococcal Cassette Chromosome mec) type III lineage formed strong biofilms in TSB supplemented with glucose and NaCl. Links between biofilm formation and accessory gene regulator (agr) status, as assessed by δ-toxin production, and with mannitol fermentation were not found. Our results show that TSB supplemented with 1.0% glucose supports robust biofilm production and reproducible quantification of S. aureus biofilm formation in vitro, whereas additional NaCl results in major variations in measurements of biofilm formation.

https://www.mdpi.com/2077-0383/8/11/1853/pdf

Biofilm Formation by Staphylococcus aureus Clinical Isolates is Differentially Affected by Glucose and Sodium Chloride Supplemented Culture Media.

A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated with Ruminococcus gnavus E1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenic Clostridia and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain R. gnavus E1 as a relevant probiotic for gut health enhancement.

https://advances.sciencemag.org/content/advances/5/9/eaaw9969.full.pdf

Ruminococcin C, a promising antibiotic produced by a human gut symbiont

Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.

/pdf/the-rumen-microbiome-an-underexplored-resource-for-novel-105yyn4nby.pdf

The rumen microbiome: an underexplored resource for novel antimicrobial discovery

Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, 2 and 3) were effective against numerous bacterial pathogens, including methicillin resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.

https://www.biorxiv.org/content/biorxiv/early/2017/07/12/148221.full.pdf

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The rumen microbiome: an underexplored resource for novel antimicrobial discovery

The rumen microbiome: an underexplored resource for novel antimicrobial discovery