There's more than meets the eye- or the gut- in Cholera infection outcome by Sara Sampaio https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz Made by Bernice Liu, Rachel Igbokwe, and Sara Sampaio en-us 2023-06-10 00:37:45 UTC 2023-06-11 01:31:01 UTC hello@padlet.com https://padlet.net/icons/png/1f9a0.png The Suckling Mouse Model bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619649468 Why did the authors decide to switch to suckling mice? Well, they: 
  • Better represent the human pathology of cholera
  • Better represents gene expression of cholera virulence factors during infection 
What did they find?
  • CR communities are dominant over DS
    • introducing a small amount of CR microbes into a DS animal was enough to restore a nearly CR phenotype
  • V. cholerae infection resistance is independent of the T6SS molecular machinery 
    • the T6SS was previously identified in the literature as a system that could kill murine E. coli and increase infection virulence6
    • however, the authors found that T6SS didn't alter levels of the E. coli strain in their suckling mice, so concluded that the CR microbes must manipulate another aspect of V. cholerae virulence
  • The degree of pathogen colonization resistance and infection outcome is highly dependent on the individual 
    • since the Bangladeshi sample had higher inter-personal variation (i.e., higher beta diversity), endemic areas may contain higher levels of infection resistance variation 
]]> 2023-06-10 00:39:57 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619649468 Article Critiques and Future Directions sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619649615 2023-06-10 00:40:36 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619649615 What is Cholera? rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619653765 Cholera is a widespread disease in the intestine caused by V. cholerae infection.1

Although Cholera hasn't been considered a "common" disease in most industrialized countries for a long time, it still is very prominent in developing countries like Bangladesh, Pakistan, Syria, and so on.2 ]]> 2023-06-10 00:55:42 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619653765 Original Paper rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619654593 2023-06-10 00:58:49 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619654593 What is V. cholerae? rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619654756 Vibrio Cholerae, or V. cholerae, is a gram-negative bacteria that resides in aquatic reservoirs, and thrives in brackish, salt, and fresh waters.4
  • V. cholerae gets introduced into the body through drinking water or consuming fish and seafood.
  • As mentioned before, Cholera is a notable health concern in developing countries experiencing contaminated drinking water systems, poor sanitation, and reduced access to healthcare.3
  • V. cholerae is abundant is such contaminated regions, which often results in annual Cholera outbreaks.
]]> 2023-06-10 00:59:20 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619654756 Major Findings bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619655132 2023-06-10 01:00:41 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619655132 Annual Cholera Cases rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619661042 Incidence of Cholera cases (including estimated cases of acute watery diarrhea (AWD)) per 100,000 population reported to WHO from 1 January to 30 November 2022.]]> 2023-06-10 01:17:32 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619661042 Cholera Symptoms rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619697747 People suffering from Cholera typically experience watery diarrhea and dehydration, but symptoms may become severe if not treated.3
  • Severe symptoms include frequent vomiting, low blood pressure, and muscle cramping.
]]> 2023-06-10 03:10:43 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619697747 Experimental Design Analysis sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619715302 Strengths:
  1. Both male and female subjects used
    • prevents the risk of generalizing sex-related differences
  2. Compared fecal and gastrointestinal (GI) samples 
    • fecal sampling can mask proximal GI tract differences for pathogenesis1; including both ensures specificity
  3. Implemented human microbiota in murine samples
    • demonstrated that microbial variation (between and within) hosts influences pathogen susceptibility
  4. Practised in vivo and in vitro
    • certain host cues are only observed in V. cholerae gene expression in vivo
  5. Multi-omics approach
    • allows for taxa identification (B. obeum) in animal models
  6. Randomized trials 
    • correlations between species abundance and V. cholerae colonization in random microbiome combinations increase reliability1
]]> 2023-06-10 04:21:26 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619715302 Pathogenesis of Cholera rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619725866 Cholera requires a coordinated regulation of environmental fit genes and V.cholerae virulence genes – which includes a toxin-coregulated pilus (TCP) and cholera toxin (CT).1
  • TCP helps in the adherence and colony formation of V.cholerae onto the intestine.5
  • Once V. cholerae is attached, CT release soon follows and enters the intestinal epithelial cells. 
  • This toxin release aids in the V. cholerae colonization, and the pathogenesis of Cholera.
A thorough description and visualization of cholera toxin mode of action is provided in the attached YouTube video.

]]> 2023-06-10 05:13:50 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619725866 What does other research suggest? sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619923304 2023-06-10 17:01:57 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619923304 Significance of Major Findings sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619923964 2023-06-10 17:03:52 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619923964 Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health (2021) sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619930182
  • Patients with inflammatory bowel disease (IBD) and type 2 diabetes showed reduced bsh enzyme expression
  • Patients with relapsing C. difficile infection (CDI) had increased taurocholic acid (TCA) levels 
    • Consistent with Alavi et al. (2020): reduced TC levels were associated with "healthy" human microbiomes, whereas high TC levels induced virulence of V. cholerae
  • These patients also exhibited decreased BSH-producing species10
    • Alavi et al. (2020): B. obeum (encodes for bile salt hydrolases) abundance was also reduced in colonized microbiomes
    • ]]>     2023-06-10 17:25:14 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619930182     Quick Overview bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619930391
  • microbiome variation and infection resistance 
  • the suckling mouse model
  • microbe randomization pipeline
  • intestinal signals and virulence gene activation
  • B. obeum bile salt hydrolase 

    • ]]>     2023-06-10 17:26:09 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619930391     Intestinal colonization against Vibrio cholerae: host and microbial resistance mechanisms (2023) sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619935089 “The observations have shown that V. cholerae is highly tolerant of conjugated bile toxicity and that in the presence of conjugated bile acids and its amino acid component, the pathogen activates several virulence genes.”

    • Similarly, Muhammad et al. (2023) concluded that V. cholerae pathogenesis is mediated by bile acids
    • They propose that virulence is induced by lowering the permeability of cell membranes to bile salts8
    • In recovering cholera patients, autoinducer-2 (AI-2) is also noted to prevent further colonization by V. cholerae
    ]]>     2023-06-10 17:45:45 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619935089     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619938329 Virulence during early infection
    • Cholera patients first experience diarrhea, which rids the intestine of crucial commensal species and bile metabolites
    • Subsequent bile production will result in increased TC levels, which influence virulence8 
    • Identification of B. obeum as a key antagonist of colonization emphasizes its required presence before V. cholerae can diminish bsh activity
    ]]>     2023-06-10 17:59:22 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619938329     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619963471 Malnutrition and Dysbiosis
    • The microbiomes of the Bangladesh cohort showed limited diversity and significant dysbiosis
    • Besides cholera, this could be due to malnutrition, a condition common in cholera-endemic regions1
    • Individuals are predisposed to heightened vulnerability, emphasizing that dysbiotic microbiomes increase susceptibility to infection
    ]]>     2023-06-10 19:37:55 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619963471     The next step bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619965639 Now that we've laid out what's been done before and which overall directions we need to go in, the next step is to identify commensal microbe species that are correlated with V. cholerae infection]]> 2023-06-10 19:46:05 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619965639 Randomization of microbe species bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619966198 Why randomization? 
    • fecal sampling is the most obvious, but the authors found that it masks critical features of the species that could affect disease pathogenesis
    • importantly, the species found in the small intestine (SI) and feces are different for CR microbes
    How they did it: 
    • take five species randomly from both CR and DS strains 
    • inject into suckling mice (either affected or unaffected with cholera) 
    • see which species correlate the most against V. cholerae infection via a combinatorial strategy
      • identify good targets for intervention 
    Findings: 
    • the only CR species that consistently correlated against V. cholerae infection was Blautia obeum (B. obeum) 
    • all DS microbes correlated positively with V. cholerae levels (Fig 5D) 
    ]]>     2023-06-10 19:48:49 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619966198     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619968925 Targeted Microbiome Modification
    • When the authors mixed CR and DS communities, resistance colonization was restored
    • Even in severely dysbiotic microbiomes, administration of SR microbial species rescued most inhibitory functions1
    • The results suggest that modifying the microbiome could be a promising approach to preventing cholera colonization or alleviating associated symptoms, as opposed to common antibiotic treatments for relapsing patients
    ]]>     2023-06-10 19:59:45 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619968925     B. obeum bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619969784 What does B. obeum do?
    • its presence statistically reduces V. cholerae colonization, but doesn't reduce the amount of the pathogen present 
    • these effects are dominant and generalizable across various gut microbiomes

    How does B. obeum do this? 
    • it depletes virulence-activating signals by producing AI-2, which downregulates TCP
    • it produces a bile salt hydrolase (bsh) enzyme that degrades virulence-activating signals in the gut
    ]]>     2023-06-10 20:03:39 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619969784     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972106 2023-06-10 20:13:33 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972106 Main Purpose rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972178 To tackle this gap in knowledge, Alavi et al used different methods and models to assess how microbial diversity affects resistance or susceptibility to intestinal pathogens, with its main focus on V. cholerae. 
    • The results from these experiments prove that a specific microbial species shape the gut’s environment via bile salt hydrolase to reduce Cholera infection risk.
    • To consider individualized microbiome variation, Alavi et al steered away from a “dichotomous” comparison of a “normal” versus “dysbiotic” microbiome.
    • These findings can aid in creating Cholera prevention strategies that are unique to the individual. 
    ]]>     2023-06-10 20:13:55 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972178     Previous Studies rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972329 Previously published scientific papers have studied the gut microbiome in response to V. cholerae infection. Other papers also show how the gut microbiome differs in people with Cholera versus those that don’t experience cholera symptoms.1
    • But the effect of interpersonal microbiome variation on pathogen resistance and susceptibility has yet to be explored.  
    ]]>     2023-06-10 20:14:36 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619972329     B. obeum and bsh enzymes bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619977690 Since TC is the most common bile acid and has several relevant characteristics regarding V. cholerae virulence, the authors wanted to see the effect CR and DS communities had on it

    Method: measured each species' ability to induce PtcpA by incubating TC solutions with pure CR and DS cultures

    Results: CR (and SR) species were better at preventing TCP gene activation because they efficiently processed TC to CA, maintaining a low TC:CA ratio 
    • B. obeum was found to be a particularly important species involved in this processing
    ]]>     2023-06-10 20:41:18 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619977690     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978128 Interpersonal Variation - the microbiome is not black and white
    • The authors emphasize differences among and within host microbiomes that can dictate infection outcomes
    • Avoids using a dichotomous lens on the microbiome, i.e. "healthy" vs. "unhealthy", treated with antibiotics or untreated, etc. that is common in the field
    • These novel perspectives demonstrate the clinical applications of host uniqueness, and better the journey towards personalized medicine
    ]]>     2023-06-10 20:42:16 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978128     B. obeum and AI-2 bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978178 After the identification of B. obeum as a potential driver of V. cholerae colonization resistance, the authors strove to determine the molecular mechanisms underlying its action

    Previous studies identified that the AI-2 autoinducer produced by B. obeum downregulates the expression of TCP biogenesis genes during infection, and cues from both host and commensal species can regulate V. cholerae gene expression in vivo

    With this in mind, the authors looked to see if there was a connection between the molecular mechanism and B. obeum-induced colonization resistance

    Method: mimic in vivo conditions for virulence gene regulation via anaerobic incubation of suckling mice intestinal tissue with a V. cholerae resistance reporter ex vivo

    Result: ablated tcpA expression in samples containing B. obeum

    However!

    A control experiment involving boiling samples of B. obeum-incubated to remove the heat-labile AI-2 still remained unable to induce tcpA --> there must be another heat-resistant mechanism at play here]]>     2023-06-10 20:42:29 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978178     Cholera Toxin Mode of Action rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978364 2023-06-10 20:43:19 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978364 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978999 2023-06-10 20:46:10 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619978999 Dysbiotic Microbiomes in response to V. cholerae rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619982662 Alavi et al. studied microbiome variation on pathogen resistance by creating two methods through reconstituting the human gut microbiome into V. cholerae animal models:
    1. Complete human fecal microbiomes. 
    2. Constructed defined gut communities using cultured human isolates.
    The use of cultured microbes is the big difference between these two methods --> ensures that the microbes’ effect was factual and takes the natural context into consideration.

    Complete fecal microbiomes from healthy American adults (contol) and previously published Bangladeshi (disease) samples were compared.
    • Alavi et al noticed that their microbial compositions were distinct, in which the Bangladeshi disease state was highly dysbiotic, had low-diversity microbial content, and dominated by the Streptococci strain
    • Even the microbiomes of healthy Bangladeshi adults had a microbial community composition similar to cholera-infected communities. 

    Diarrhea, dehydration, and malnutrition are common in developing countries, and may also push one’s microbiome to a dysbiotic state.
    • Therefore, they hypothesized that the distinct microbiome dysbiosis during diarrhea recovery may be a recurring window of vulnerability to cholera. 

    ]]>     2023-06-10 21:04:28 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619982662     Acknowledgements bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619987973
  • Bernice Liu: Major Findings (minus "Dysbiotic Microbiomes in response to V. cholerae", and "Microbiome Modification restores Colonization Resistance"). 
  • Rachel Igbokwe: Introduction and Cholera Background Information, Major Findings (only "Dysbiotic Microbiomes in response to V. cholerae", and "Microbiome Modification restores Colonization Resistance").
  • Sara Sampaio: Article Critiques and Future Directions 
    • ]]>     2023-06-10 21:32:26 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619987973     Microbiome Modification restores Colonization Resistance rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619988580 Alavi et al then used cultured human isolates to create two defined gut communities:
    1. CR (the "healthy state") – characterized by a high taxonomic diversity, consists of Bacteroides, Clostridium, and Blautia.
    2. DS (the "dysbiotic state") – characterized by a low taxonomic diversity, consists of Streptococci, E.coli, Enterococcus faecalis.

    These cultures were administered into germ-free mice.
    • Alavi et al observed the mice receiving CR cultures were resistant to V. cholerae colonization in the small intestine.

    They also made a third “mixed group” that involved the administration of a 1:1 mixture of CR and DS cultures into germ-free mice. 
    • This mixed group experienced lower V. cholerae levels than the DS group, and dropped even lower than the CR group two days after infection.

    These two experiments highlighted the significance of interspecies and inter-individual microbiome variation in pathogen susceptibility. 
    • The mixed group demonstrates that colonization resistance can be restored through microbiome modification. 

    ]]>     2023-06-10 21:35:32 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619988580     Remaining Questions & Next Steps sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619988849 2023-06-10 21:37:11 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619988849 Are there additive effects on pathogenesis? sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619989640
  • No significant additive effects were observed on V. cholerae abundance when B. vulgatus or C. scindens were added to pure cultures containing B. obeum
  • AI-2 could play a role in suppressing colonization via downregulation of TCP expression (↓ TCP biogenesis)
    • ]]>     2023-06-10 21:41:45 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619989640     B. obeum was sufficient to ablate tcpA expression without AI-2 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619990010 2023-06-10 21:43:59 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619990010 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619990678 This was from an isolated study to determine the effects of B. obeum on V. cholerae 
    • A 1 log drop in colonization with B. obeum vs 2 log-fold difference in the colonization of CR, DS microbiome suggests that additive effects are at play1
    ]]>     2023-06-10 21:47:42 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619990678     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619992596
  • Investigate quorum sensing systems that modulate TcpP activity
    • These pathways disrupt the expression of virulence factors that encode for TCP and are hypothesized to involve AI-29
  • Determine whether AI-2 and B. obeum synergize to mediate colonization in vivo (AI-2 studies were mimicked in vivo using ex vivo studies)
    • ]]>     2023-06-10 21:58:32 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619992596     Members of the human gut microbiota involved in recovery from Vibrio cholerae infection (2014) sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619994318
  • Using similar methods, the authors recognized a pattern of taxa in recovering cholera patients9
  • Identified R. obeum as a primary candidate for virulence suppression and colonization resistance instead of B. obeum 
    • ]]>     2023-06-10 22:09:47 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619994318     Bile Acids! bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619994783
  • heat resistant
  • spend a long time in the SI - where B. obeum is!
  • human bile acids are commonly conjugated to amino acids like taurine and glycine 
  • these conjugated acids like Taurocholate (TC) can induce tcp virulence gene expression 
  • commensal microbes encode for bile salt hydrolase (bsh) enzymes which are critical for bile acid metabolism 
    • ]]>     2023-06-10 22:12:27 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619994783     Introduction and Cholera Background Information rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619996103 2023-06-10 22:20:39 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619996103 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619996412 Studies have transferred R. obeum to the genus Blautia, meaning these strains are virtually the same in function11
    • Moreover, the study used samples from Bangladesh children
      • Children's microbiomes are neither fully developed nor stable, meaning the findings of this paper may not be fully indicative of infection outcomes in the general Bangladeshi public 
    ]]>     2023-06-10 22:22:45 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619996412     Taurocholate (TC) bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619997435
  • the most common bile compound
  • conjugated to the amino acid taurine 
  • can induce tcp gene expression - induces virulence 
    • modulates upstream virulence activator in V. cholerae TcpP 
    • activates PtcpA
  • de-conjugated compound is cholic acid (CA) 
    • neutral - doesn't activate PtcpA 
    • ]]>     2023-06-10 22:29:20 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619997435     Does diet impact infection resistance? sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619999377
  • Concept has not been well studied and becomes a confounding variable for Alavi et al.
  • While interpersonal variation is the focus of this paper, the distance and therefore dramatic differences between the lifestyles of each cohort must be taken into consideration
    • Factors such as climate, agriculture, medical practices, political regimes, and cultural differences all contribute to the composition of the microbiome 
    • ]]>     2023-06-10 22:42:09 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2619999377     Redesign experiment to analyze samples from more geographically-similar places sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620001799 For example, 
    • Compare the US cohort to one from the Dominican Republic, a country with a (recent) history of cholera outbreaks2
    • Compare Bangladesh citizens to a non-endemic country in South-East Asia like Singapore
    ]]>     2023-06-10 22:59:30 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620001799     sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620002348 Enough distance is maintained to ensure interpersonal variation in microbiome and diet, but not so drastically that external factors become significant confounding variables! ]]> 2023-06-10 23:02:01 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620002348 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620003076 2023-06-10 23:07:18 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620003076 sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620004772 Weaknesses:
    •  Discrepancies between U.S. and Bangladesh samples
      • U.S. cohort had extensive qualifications (thorough inclusion/exclusion criteria)
        • e.g. participants could not have active GI disorders, systematic antibiotic use, acute illness, etc.1
      • Bangladesh sample was from pre-sequenced data from a 2014 study9
        • reduced experimental manipulations for cholera-endemic regions may cause other confounding variables to be overlooked (e.g. additional health concerns, genetic predispositions), providing an inaccurate representation of the population
    ]]>     2023-06-10 23:18:35 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620004772     B. obeum encodes type 1 bsh enzymes bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620005013 Next, the authors examined genetic determinants of bile acid processing to determine the molecular basis for B. obeum’s effect on TC-dependent virulence induction

    Results:
    • a previous study classified bsh enzymes into different phylotypes based on sequence similarity, showing that different types have various substrate-dependent deconjugation actions7 
    • B. obeum is predicted to encode for bsh type 1 enzymes, which are the most effective at deconjugating TC and other potent activators of tcpA expression in V. cholerae
      • Additionally, most CR microbes encode for bsh homologs while DS microbes lack bsh genes
    • B. obeum has such a dominant effect on Vibrio resistance that pure cultures of the strain or its bsh enzyme can overpower the effect of DS microbes like S. salivarius and reduce both tcp activation by TC and TC levels directly 
    ]]>     2023-06-10 23:19:59 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620005013     Interpersonal Gut Microbiome Variation? rachelseats7 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620006734 2023-06-10 23:32:19 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620006734 bsh levels in human gut microbial communities are correlated to V. cholerae infection outcome bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620008580 Finally, the authors sought to determine the distribution of the bsh phylotypes in healthy and dysbiotic human gut microbiomes

    Method: analyzed a previously published shotgun sequencing metagenomic dataset of Bangladeshi cholera patient gut microbiomes

    Results: 
    • bsh levels were already affected by diarrhea prior to any treatment (antibiotics) 
      • depleted phylotypes 1, 3, 4, 5
      • phylotypes highly active against TC: 1, 3, 4 
    • So, a characteristic of healthy human microbiomes that may affect v. cholerae susceptibility is their ability to deconjugate TC into a non-virulence-inducing form (like CA)
    ]]>     2023-06-10 23:44:11 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620008580     Findings: Summary bernicehyliu https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620013819
  • a mixed CR + DS group demonstrates that CR microbes have a dominant effect and colonization resistance can be restored through microbiome modification
  • the degree of pathogen colonization resistance and infection outcome is highly dependent on the individual 
  • B. obeum abundance and bsh activity is associated with increased V. cholerae colonization resistance 
    • ]]>     2023-06-11 00:14:12 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620013819     References sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620020622
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    7. Song Z, Cai Y, Lao X, Wang X, Lin X, Cui Y, Kalavagunta PK, Liao J, Jin L, Shang J, et al. Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome. Microbiome. 2019;7(1). doi:https://doi.org/10.1186/s40168-019-0628-3

    8. Abdullahi Yusuf Muhammad, Amonov M, Chandrika Murugaiah, Atif Amin Baig, Yusoff M. Intestinal colonization against Vibrio cholerae: host and microbial resistance mechanisms. AIMS Microbiology. 2023 [accessed 2023 Jun 7];9(2):346–374. doi:https://doi.org/10.3934/microbiol.2023019

    9. Hsiao A, Ahmed AMS, Subramanian S, Griffin NW, Drewry LL, Petri WA, Haque R, Ahmed T, Gordon JI. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature. 2014 [accessed 2019 Nov 27];515(7527):423–426. https://www.nature.com/articles/nature13738. doi:https://doi.org/10.1038/nature13738

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    ]]>     2023-06-11 00:54:40 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620020622     Major Findings Continued sarasampaio2 https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620023810 2023-06-11 01:14:22 UTC https://padlet.com/sarasampaio2/33hs97xjkg9zg9gz/wish/2620023810