Cystic fibrosis pulmonary exacerbations (CFPEs) compound the severity of pulmonary function decline that leads to 90% of CF patient mortalities. Determining the microbial drivers of CFPEs represents a key step towards preventing and treating exacerbations. Standard methods for treating CFPEs utilize broad-spectrum antimicrobial therapy to target conventional pathogens such as P. aeruginosa. In addition to the conventional pathogens, CF infections are influenced by diverse microorganisms, rendering them polymicrobial in nature. The rapid establishment of next-generation sequencing techniques has enabled profiling of these communities using the ‘omics.
In a recent study, the Forest Rohwer lab developed the Cystic Fibrosis Rapid Response (CFRR). CFRR utilizes viromics, metagenomics, metatranscriptomics, and metabolomics data to monitor the microbiomes of CF airways over the course of a CFPE. To support the use of CFRR in the clinic, the lab presented a case study of a CF patient experiencing a fatal pulmonary exacerbation. This patient’s microbiome comprised of the established pathogen P. aeruginosa in the days before his death. More interestingly, the study also identified E. coli as a prominent member of the CF lung during the patient’s fatal exacerbation. Using a combination of metatranscriptomics, metagenomics, and metabolomics, the study determined that this E. coli population expressed Shiga toxins that may have been released prior to the fatal exacerbation.
Overall, the study provides an example of the ways through which the ‘omics provides clinicians information to make decisions when treating CF patients. The CFRR pipeline demonstrates potential for the rapid identification of the microbes that contribute to CFPE onset.
Please join us on Friday May 24th 2019 in HSC 3N10A to discuss the findings of this paper and the following:
- Evaluate a case study for using the ‘omics within clinical contexts
- Identify possible gaps and strategies towards translating ‘omics data for treating pulmonary disease
While the composition of the microbiome in various conditions is often the focus of studies, little is known about the evolutionary dynamics of commensurable in healthy people. Evolution in complex communities such as the gut microbiome is complex and tracking adaptive evolution in commensal bacteria can provide insight as to the important factors for long term colonization in the the gut.
In their recent paper, Zhao et al. studied adaptive mutations in Bacteroides fragilis lineages from healthy donors over time and across populations. They identified several key genes that underwent parallel evolution as well as specific lineages co-existing over time. Such parallel evolution was found both in multiple sublineages in a single donor (person specific selection) or across multiple donor (general selection). Also, an active prophage was found to be responsible for the co-evolution of twospecific sub-lineages. They also found an over representation of a specific mutation in Western populations compared to Chinese populations, indicating a population specific.
Overall, this study demonstrate how adaptive evolution tracking can be used to find important target for colonization which has implication in various microbiome related fields such as microbiome manipulation, therapies and probiotics.
Please join us on Friday April 26th, 2019 at 3:00PM in HSC 3N10A to discuss the findings presented in this paper.
Paper Citation: Zhao, S. et al. Adaptive Evolution within Gut Microbiomes of Healthy People. Cell Host & Microbe (2019). doi:10.1016/j.chom.2019.03.007
Breast milk is a primary source of nutrition for infants in their first months and plays a large role in shaping the infant gut microbiota. However, the composition and determinants of the milk microbiota are not well understood. In their recent work, Moossavi et al. examined factors that influence the microbial content of breast milk. They studied data from 393 mother–baby pairs, where some mothers exclusively nursed their infants at the breast and others used a mechanical breast pump to collect milk. They identified mode of breastfeeding as a key determinant of milk microbiota composition and determined that milk microbiota variability is affected by maternal factors and other milk components. Additionally, their work supports the retrograde inoculation hypothesis, where the bacteria present in the infant’s oral cavity impacts the composition of the milk microbiota. Overall, the results presented in their work help elucidate features of the human milk microbiota composition, which could have potential implications for infant health.
Please join us on Friday March 22nd, 2019 at 3:00PM in HSC 3N10A to discuss the findings presented in this paper.
Paper Citation: Moossavi, S., Sepehri, S., Robertson, B., Bode, L., Goruk, S., Field, C. J., … & Turvey, S. E. (2019). Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell host & microbe, 25(2), 324-335.
The burden of
influenza is a complex problem and has been long recognized as a significant
cause of morbidity and mortality in human populations. A crippling 3500 deaths
in Canada are estimated to be caused by influenza, with approximately 10 billion
dollars being the consequent economic burden. This has lead to the subsequent development of
vaccines in order to reduce resulting health and economic burdens. There is
overwhelming evidence indicating that the influenza virus infection leads to
acute infection both in the upper and lower respiratory tracts. Unsurprisingly,
there are a plethora of factors that influence one’s susceptibility to the
In this paper by Lee et.al, data from a longitudinal household transmission study and proceeding generalized linear mixed effects models were used in order to study the influences of the nose and throat microbiota and the susceptibility to influenza infection. Untargeted 16S rRNA taxonomic screening was conducted to determine bacterial community “state types” concluding that it was associated with lower susceptibility to influenza virus infection. The study also demonstrates a strong association between age and the prevalence and stability of the nose/throat bacterial communities.
join us on Friday February 22nd, 2019 at 3:00PM in HSC 3N10A to examine the
findings of this paper and discuss:
relationship between the nose/throat microbiota and the flu
- How the flu alters
the bacterial community
There is still debate among scientists about whether or not to publicly release their painstakingly collected data once the main analysis is complete. Opinion on either side can get heated with major repercussions for the community at large. Luckily, many groups are able to deposit their raw sequencing data and as such, reams of metagenomic data are now publicly available from many human body sites from people around the world. Savvy computational biologists and bioinformaticians are making great use of that data to generate tools and resources that help us all.
This week we’ll discuss a microbiome paper that was published as a Cell press Resource. The computation labs of Nicola Segata and Curtis Huttenhower teamed up with Maria Carmen Collado, Xochitl Morgan and Chris Quince for the Hurculean task of mining 10,000 human metagenomes to reconstruct as many bacterial and archaeal genomes as they could. You can find the paper here: https://www.sciencedirect.com/science/article/pii/S0092867419300017.
The paper itself is too long to analyse fully but I will go over questions like:
- What methods did they use?
- What did they uncover?
- How does this resource add to our research?
Journal club will be held January 25th at 3pm in MUMC 3N10A. No need to read the whole paper or be an expert in metagenomics to contribute, all are welcome!
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!
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.
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
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.
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!
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.