Biology subjects

Narbad, A.

Publications and source records attributed to Narbad, A..

8 recordsLinked to original sources

bioRxiv2024

Bacteroides thetaiotaomicron enhances H2S production in Bilophila wadsworthia

Sulfate- and sulfite-reducing bacteria (SRB) are a group of strict anaerobes found within the human gut. Bilophila wadsworthia, a sulfite-reducing bacterium which produces hydrogen sulfide (H2S) from taurine and isethionate respiration is a common member of the healthy commensal human gut microbiota, but has been implicated in several disease states including inflammatory bowel disease and colorectal cancer. Bacteroides thetaiotaomicron, one of the most prominent gut bacteria, has sulfatases which release sulfate, serving as a potential substrate for sulfate-reducing bacteria. Here, we showed that when B. thetaiotaomicron and B. wadsworthia were in co-culture, there was a significant increase in B. thetaiotaomicrons growth and in H2S production by B. wadsworthia. Differential gene expression analysis revealed increased expression of B. wadsworthias dsrMKJOP complex in co-culture, which delivers electrons for sulfite reduction to H2S. This was accompanied by a decreased expression of genes associated with taurine, sulfolactate and thiosulfate respiration, indicating that B. thetaiotaomicron may provide an alternative source of sulfite to B. wadsworthia. We hypothesised adenosine 5-phosphosulfate (APS) to be this intermediate. Indeed, B. wadsworthia was able to grow using APS or sulfite as electron acceptors. Endometabolomic and transcriptomic analyses revealed decreased production of indole by B. thetaiotaomicron in co-culture with B. wadsworthia due to enhanced tryptophan utilisation by B. wadsworthia. The results of this microbe-microbe interaction could have significant pro-inflammatory effects in the human gut environment.

microbiology↗

bioRxiv2023

Machine learning-based meta-analysis reveals gut microbiome alterations associated with Parkinson's disease

There is strong interest in exploring the potential of the gut microbiome for Parkinsons disease (PD) diagnosis and treatment. However, a consensus on the microbiome features associated with PD and a multi-study assessment of their diagnostic value is lacking. Here, we present a machine learning meta-analysis of PD microbiome studies of unprecedented scale (including 4,490 samples). Within most studies, microbiome-based machine learning models could accurately classify PD patients. However, models were study-specific and did not generalise well across other studies. By training models on multiple datasets, we could improve their general applicability and disease specificity as assessed against microbiomes from other neurodegenerative diseases. Meta-analysis of shotgun metagenomes moreover delineated PD-associated microbial pathways potentially contributing to the deterioration of gut health and favouring the translocation of pathogenic molecules along the gut-brain axis. Strikingly, diverse microbial pathways for the biotransformation of solvents and pesticides were enriched in PD. These results align with the epidemiological evidence that exposure to these molecules increases PD risk and raise the question of whether gut microbial metabolism modulates their toxicity. Taken together, we offer the most comprehensive overview to date about the PD gut microbiome and provide future reference for its diagnostic and functional potential.

microbiology↗

bioRxiv2020

Desulfovibrio diazotrophica sp. nov., a sulphate reducing bacterium from the human gut capable of nitrogen fixation

Sulphate-reducing bacteria (SRB) are widespread in human guts, yet their expansion has been linked to colonic diseases. We report the isolation, genome sequencing, and physiological characterisation of a novel SRB species belonging to the class Deltaproteobacteria (QI0027T). Phylogenomic analysis revealed that the QI0027T strain belongs to the genus Desulfovibrio with its closest relative being Desulfovibrio legallii. Metagenomic sequencing of stool samples from 45 individuals, as well as comparison with 1690 Desulfovibrionaceae metagenome-assembled genomes, revealed the presence of QI0027T in at least 22 further individuals. QI0027T encoded nitrogen fixation genes and based on the acetylene reduction assay, actively fixed nitrogen. Transcriptomics revealed that QI0027T overexpressed 45 genes in nitrogen limiting conditions as compared to cultures supplemented with ammonia, including nitrogenases, an urea uptake system and the urease enzyme complex. To the best of our knowledge, this is the first Desulfovibrio human isolate for which nitrogen fixation has been demonstrated. This isolate was named Desulfovibrio diazotrophica sp. nov., referring to its ability to fix nitrogen ( diazotroph). ImportanceAnimals are often nitrogen limited and have evolved diverse strategies to capture biologically active nitrogen. These strategies range from amino acid transporters to stable associations with beneficial microbes that can provide fixed nitrogen. Although frequently thought as a nutrient-rich environment, nitrogen fixation can occur in the human gut of some populations, but so far it has been attributed mainly to Clostridia and Klebsiella based on sequencing. We have cultivated a novel Desulfovibrio from human gut origin which encoded, expressed and actively used nitrogen fixation genes, suggesting that some sulphate reducing bacteria could also play a role in the availability of nitrogen in the gut.

microbiology↗

bioRxiv2019

Faecal microbiota transplant from aged donor mice into young recipients affects spatial learning and memory

BackgroundThe gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems, however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients affected the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process, and related functions. Methods and FindingsYoung adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. Gut permeability, levels of circulating cytokines and expression of markers of microglia cells were also assessed. FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype, while gut permeability and levels of circulating cytokines remained unaffected. ConclusionsThese results demonstrate a direct effect of the age-associated shifts of the microbiota on protein expression and key functions of the central nervous system. Furthermore, these results additionally highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions in the elderly.

neuroscience↗

bioRxiv2019

Production of multiple bacteriocins, including the novel bacteriocin gassericin M, by Lactobacillus gasseri LM19, a strain isolated from human milk

Bacteriocins are antimicrobial peptides produced by bacteria and their production by health-promoting microbes is regarded as a desirable probiotic trait. We found that Lactobacillus gasseri LM19, a strain isolated from human milk, exhibits antagonistic activity against different enteropathogens and produces several bacteriocins, including a novel bacteriocin, gassericin M. These bacteriocins were purified from culture and synthesised to investigate their activity and potential synergy. L. gasseri LM19 was tested in a complex environment mimicking human colon conditions where it not only survived but expressed the seven bacteriocin genes and produced short chain fatty acids. Metagenomic analysis of these in vitro colon cultures showed that co-inoculation of L. gasseri LM19 with Clostridium perfringens gave profiles with more similarity to controls than to vessels inoculated with C. perfringens alone. This makes L. gasseri LM19 an interesting candidate for further study for maintaining homeostasis in the gut environment.

microbiology↗

bioRxiv2019

First evidence of production of the lantibiotic nisin P

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. Here we describe Streptococcus agalactiae DPC7040, a human fecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a fecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.

microbiology↗

bioRxiv2018

Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimers disease. Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR, APOE3 and APOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in group-aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, the findings indicate that APOE genotype associated with specific gut microbiome profiles in both humans and in APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention and treatment of AD.

genomics↗

bioRxiv2017

Bacteria facilitate viral co-infection of mammalian cells and promote genetic recombination

Intestinal bacteria promote infection of several mammalian enteric viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact enteric viruses. We found that most bacterial strains bound poliovirus, a model enteric virus. Given that each bacterium bound multiple virions, we hypothesized that bacteria may deliver multiple viral genomes to a mammalian cell even when very few virions are present, such as during the first replication cycle after inter-host transmission. We found that exposure to certain bacterial strains increased viral co-infection even when the ratio of virus to host cells was low. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated viral fitness restoration through genetic recombination. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

microbiology↗