The new Journal Club schedule is up

See the Journal Club page for the 2019 schedule of speakers. As usual the topics are posted the week before we meet to stay tuned and see you next year!

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Microbiota-mediated mechanism of colonization resistance to enteric pathogen Salmonella enterica serovar Typhimurium

The microbiome is essential for numerous features of host physiology, including metabolism (by degrading otherwise non-digestible molecules), immune maturation and homeostasis and resistance to infection (e.g., via colonization resistance). Despite the profound effect of gut microbes on human overall health, the mechanisms involved in this complex network of microbial interactions, included within the human microbiome and between pathogen and host-associated microbial communities, remained mostly unknown. For instance, it has been demonstrated that the members of the gut microbiota confer colonization resistance, however, the direct microbial interactions and the metabolites involved in this complex phenomenon have not been extensively investigated.

A recent study performed by Dr. Denise Monack’s research group at Stanford University has proposed a mechanism explaining colonization resistance to Salmonella enterica serovar Typhimurium by Bacteroides species, common members of the gut microbiota. They demonstrated that propionate (microbial metabolite part of the short-chain fatty acid family) is acting directly on the intestinal pathogen by disrupting intracellular pH homeostasis and hence resulting in bacterial death. Moreover, this study was performed in an unperturbed ecosystem and emphasizes the importance of that a single metabolite could have on the host tissue homeostasis.

Please join us on Friday, November 23rd, 3-4 pm in MUMC 3N10A to discuss this paper.

Paper citation:

Jacobson A, Lam L, Rajendram M, Tamburini F, Honeycutt J, Pham T, et al. A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection. Cell Host and Microbe. 2018

DOI:10.1016/j.chom.2018.07.002

 

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Are we ready to monitor the microbial composition associated to severity and clinical remission in patients with ulcerative colitis?

Recent insights into the molecular pathogenesis of inflammatory bowel disease (IBD) point to a complex interplay of susceptibility genes, aberrant immune responses and environmental factors as triggers of the disease. Several studies imply that specific bacteria and bacterial products play a role in the onset and in the subsequent disease progression of ulcerative colitis (UC), one of the most frequent forms of IBD. However, it is not well elucidated whether a characteristic IBD pathogenic microbiota exist. Schimer et al. have investigated the role of gut microbiome in pediatric new-onset, treatment-naive UC patients treated with two conventional therapies (5ASA mesalamine or corticosteroids followed by mesalamine). The authors observed taxonomic shifts prior to treatment initiation associating with disease severity and progression, including remission and colectomy. Extensive microbial depletion and expansion of bacteria typical of the oral cavity were linked to severe disease in treatment-naïve patients and the restoration of this imbalance was linked to improved disease severity and, potentially, favored remission. Treatment with corticosteroids significantly impacted gut microbial composition, with secondary differences associated to responsiveness to the drug. In addition, they have also shown that UC fecal microbiota overlap with rectal biopsy microbiota profile, both associating with specific serological markers of disease progression. This study suggests potential interactions between the gut microbiome and the immune system at the antibody level that might be of interest for disease diagnostic. In conclusion, the authors have provided evidences of the strong association between gut microbiome, disease progression and treatment efficacy, which might transform clinical practices and inform optimal treatment strategies, such as the implementation of more aggressive treatment regimen for patients at higher risk of progressive disease.

Please join us on Friday November 2nd, 2018 at 3:00PM in HSC 3N10A to examine the main findings of this paper.

Schirmer M, Denson L, et al. Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course. Cell Host Microbe. 2018 Oct 10;24(4):600-610.e4. doi: 10.1016/j.chom.2018.09.009.

https://www.ncbi.nlm.nih.gov/pubmed/30308161

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October journal club will be moved to Nov 2

This week’s journal club will be postponed until next Friday where Alberto Caminero will talk to us about the microbiome and Celiac disease. Until then have a happy Halloween!

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The gut mucosal colonization with probiotics might not be as effective as you think!

 

While the probiotic industry is rapidly growing and healthy individuals are commonly using probiotics in order to boost their health, the two new studies published on CELL cast doubt on the efficacy of probiotic colonization of gut mucosa in humans and mice.

Zmora et al., 2018, Cell characterized the murine and human mucosal-associated GI microbiome using metagenomics, and found that human GI tracts show person-, region- and strain-specific mucosal colonization patterns that are predictable by pre-treatment microbiome and host features. They also found that stool only partially correlates with the microbiome functioning inside the body, so relying on stool samples alone could be misleading. On Friday, Sep 28,2018 at 3:00PM in HSC 3N10A, I’ll lead our club discussions to examine the findings of this paper. Specifically, we will discuss;

Resistance and susceptibility to probiotic colonization in the gut mucosa of humans and mice.

Predictable probiotic colonization using microbiome and host features.

The human and mice gut mucosal microbiome and their correlation with stool.

 

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Diversity promotes diversity: The gut microbiome increases genetic drift of bacteriophages

Bateriophages are often studied in relation to their bacterial host. A recent surge of interest in the microbiome have given rise to more broad studies of the virome using various -omics techniques. However both these approaches are only a part of the picture and in order to gain a better understanding of the role phages play in the human microbiome, a more holistic approach is necessary.

image description

Graphical abstract, De Sordi et. al 2017, Cell Host & Microbe

In this 2017 paper by De Sordi et. al. the French team studied the evolution of phages both in vitro and in vivo in the mouse gut microbiome. By adding phage to defined co-cultures containing the host and a resistant strain (in vitro and in a dixenic mouse model) and to a normal microbiome (containing the same two strain) they were able to observe in the microbiome cultures what they call a viral host jump, a change in the host strain of the phage. This challenges the idea that the fate of phages is tied to that of their host and offers a mechanism explaining the persistence of phages in complex environment.

 

Please join us on Friday August 24th, 2018 at 3:00PM in HSC 3N10A to examine the findings of this paper and discuss:
1. Phage/Bacteria co-evolution
2. The gut microbiome as a driver of changes in bacterial virus diversity
3. What these findings mean for the classification /speciation of viruses

Paper citation:
De Sordi, L., Khanna, V. & Debarbieux, L. The Gut Microbiota Facilitates Drifts in the Genetic Diversity and Infectivity of Bacterial Viruses. Cell Host Microbe 22, 801–808.e3 (2017). https://doi.org/10.1016/J.CHOM.2017.10.010

 

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Identifying Influential Antibiotic Resistance Genes in the Infant Gut Microbiome via Machine Learning Techniques

Image result for antibiotics and bacteria

CDC/Dr. JJ Farmer (PHIL #3031), 1978.

Antibiotics provide a necessary relief from infectious disease, but they also end up altering the bacterial composition of the microbiome. An initial change in the community composition occurs when the antibiotics are administered, killing off many bacteria. Then a lasting effect may occur when the new community favours bacteria with antibiotic resistant genes.

Here, Rahman et al. longitudinally sampled stool from 107 premature infants to study their gut microbiome dynamics after antibiotic use. Using machine learning techniques on the genomic data, they were able to find key genes for survival after antibiotic use. They were also able to predict how the gut microbiome would be altered after antibiotic use.
Please join us on Friday July 27th, 2018 at 3:00PM in HSC 3N10A to examine the findings of this paper and discuss:
1. Genome-resolved metagenomics
2. Gut resistome
3. Machine learning techniques

presented by Lucas Flett

Paper Citation: Rahman SF, Olm MR, Morowitz MJ, Banfield JF. 2018. Machine learning leveraging genomes from metagenomes identifies influential antibiotic resistance genes in the infant gut microbiome. mSystems 3:e00123-17. https://doi.org/10.1128/mSystems.00123-17

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Cancellation

Good morning,

Due to unforeseen circumstances, this month journal club will be canceled. Sorry for the late notice. Hope to see you all next month.
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Journal Club Update

Good afternoon,

This week journal club will be pushed to next Friday (June 29th) same time, choice of paper and room TBD. See you there.
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Bacterial viruses, more than just a proxy for the microbiome

Attempts to study the viruses of the human microbiome (virome) have followed a similar path to the study of the microbiome itself – although with a time lag due to the additional complexities of studying viruses. First, there was an exploration of what is present in humans, followed by efforts to correlate shifts in the virome to aspects of health. The field is only just beginning to work towards establishing causal links between viruses and observable phenotypes in humans.

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Summary Figure, Norman et al 2015, Cell

The 2015 Norman et al. paper in Cell was a landmark study for the field of virome research, representing one of the first rigorous approaches to virome characterization in health and disease. Through sequencing of fecal filtrates, they were able to correlate the abundance and diversity of bacterial viruses to those of the fecal bacterial community. Because bacterial viruses can only exist in the presence of their hosts, it was surprising to find that as the bacterial community became less diverse in disease, the viral community did the opposite! This discrepancy justifies the study of the viral community not simply as a proxy for the bacterial community, but also for its own potential diagnostic and therapeutic merits.

Please join us on Friday May 25th, 2018 at 3:00PM in HSC 3N10A to examine the findings of this paper and discuss:

  1. Sequencing the virome, and extracting meaningful data from it
  2. Hypotheses as to drivers of changes in bacterial virus diversity
  3. Implications of these findings on future virome research, especially in health .

Paper Citation:

Norman, J.M., Handley, S.A., Baldridge, M.T., Droit, L., Liu, C.Y., Keller, B.C., et al. (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160: 447–460 http://dx.doi.org/10.1016/j.cell.2015.01.002.

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