Josee Alonzi, Alex Fried, Jacey Larovere, Cassidy Cross
Darwinian Medicine
Bacteria As Protection
Not All Heroes Wear Capes
- Protect through recognition and tolerance
- TLRs recognize patterns that provide the ability of discriminating between pathogenic and commensal bacteria
- Oral tolerance -> less sensitive to an antigen, once ingested
- Mode of delivery determines what type of flora that colonizes the fetus' microbiome
- Possible that c-section results in weaker defence against immunity disorders
C. diff and Fecal Transplants
Diffintely Pooptastic
Interaction with the Environment
- C.diff induced diarrhea as a result of disruption of the gut microbiome
- Harmful bacteria that arises from complications with antibiotic therapy
- Fecal microbial transplantation: the transfer of stool from a healthy donor into the gastrointestinal tract of someone who is ill and in need of a replenished microbiome
- Natural birth vs. c.section
- Modern medicinal approaches increasing immune disorders?
- Societal structure change and cultural differences creating a different environment to interact with
- Increase in allergies, autoimmunity, inflammatory bowel disease, vascular disease, some cancers, depression/anxiety, and possibly some forms of autism, neurodegenerative disorders and both type 1 and 2 diabetes
- Time in which these have become evident is too short to be purely genetic, however the two may work in unison
Evolution of the Gut
Newly Discovered, Old Friends
- Microbial is based on the fitness of the host and its population
- Co-evolving and co-dependent relationship between "us" and "them"
- Comparing microbial communities among different regions and lifestyles is the next step in understanding the control of the human gut
- Disease now observed as interaction between microbiome and the environment
The Hygiene Hypothesis
Autism and Fecal Transplant
- Possible link between the microbiome and autism/ neurological disorders
- Study focused on effects of FMT
- Showed GI and ASD symptoms slowly improving
- Findings emphasized the importance of phages as protective barrier
The Microbiome
The Good, the Bad, and the Defense Mechanisms
- Microbes consist of pathogens, and non-pathogenic types, including commensals and environmental strains, and components such as bacterial endotoxins
- This bacteria is the bodies defense, targeting the lymphoid tissues that produce the antibodies to pathogens
- microbial cells: "human cells" , 10:1
- Preserves the good species in order to fight off the bad
- Fetus gut is sterile until passing through the birth canal
The Impact of Microbes on Atopic Disease
- Change in lifestyle has caused reduced exposure to infectious opportunities
- Originally stated family dynamic was responsible for exposure
- Removal from infectious opportunities is product of current public health measures
- Increase in sanitation/reduced infectious diseases is linked with an increase in immunity disorders
Current and Future Implications
- What are the mechanisms involved in the development of antibiotic resistant properties in bacteria?
- Anthropomorphic Intervention
- Occurs when a mutation develops in a population susceptible to antibiotics
- Antibiotics are introduced and the mutated cells are left uneffected while the suceptable cells die
- Only mutated, resistant cells of the original bacteria are left to reproduce
(Munita and Arias, 2016)
- Treatment for MRD's are few and ineffective
- Combination Therapy
(Izadpanah and Khalili, 2015)
- Public Health Issues
- Hospital settings provide excellent grounds for the transmission of resistant bacteria
- Poor understanding of proper antibiotic use (FDA, 2017)
How are we to combat this
issue moving forward?
Defense Mechanisms
Trade-offs naturally selected for their defense against illness and predation
Anxiety
Block Defenses?
Importance of Evolutionary viewpoint
All or None Defenses
vs.
Graded Defenses
If our defenses are expressed more frequently and intensely than required why don't we block them?
- Mechanism to prepare the body for danger
- But there has been a shift in what dangers we experience
- Evolutionary perspective allows a better understanding
- Example: stranger fear in babies
- Nesse's two models to describe the cost/benefit relationship of defense mechanisms
- Ideally defense mechanisms should be expressed to a degree near optimum need for protection
- But why do false alarms occur?
(Nesse, 2001)
- Decrease in relevance
- Trade-offs can seem like unnecessary inconvenience, discomfort, or suffering
- Possibly affect overall health and well-being
- Prolong illness
- Complications
- There are reasons defense mechanisms were selected for
(Nesse, 2001)
Candidate for Suppression?
- Errs on the side of excessive
- Can result in anxiety disorders, panic attacks, and phobias
- Negative effects on overall health
All or None
Defenses
Graded Defenses
- Defenses as continuously variable intensities
- levels of fever, frequency of cough, levels of inflammation, levels of anxiety
- Ideally the cost of defense increase linearly with the cost of expected harm
- But regulatory systems allow for costs of defense to exceed cost of expected harm
- Expression of defenses are more excessive than required
(Nesse, 2005)
- Defenses that are either fully expressed or not
- vomiting, panic attack
- Model describes expected probability of harm as a function of the expected cost of defense compared to the expected cost of harm
- The costs of all or none defenses are low
- The threshold for activating a defense is a 5% chance of harm
- This explains why we experience frequent false alarms
(Nesse, 2001)(Nesse, 2005)
Fever
Smoke Detector Principle
- In both mammals and non-mammals
- Method to combat infection by increasing core body temperature
- 37-40 degrees degrees Celsius
- Proven effective at fighting against viral and bacterial infection
- Considered a natural remedy throughout human evolution
- Randolph Nesse's principle on the regulation of defense responses
- Explains why we frequently experience "false alarms"
- The costs of too much defense out ways the costs of too little defense
(Nesse, 2001)
Consequences of Blocking Fevers
Serious Fevers
- Prolonged high core temperatures of 42.2 degrees Celsius or higher
- Cell damage, denaturing of proteins, increased inflammatory response
- Could result in convulsions, organ failure, brain damage, and death
- Can be result of heat exhaustion, inflammatory conditions, side effects from medication
(Walter et al., 2016)
- On the notion fevers can be harmful
- Use of medication or external cooling
- Benefits of cooling techniques in patients with fevers from septic shock
- But equal amount of data supporting fever suppression and the benefits of fevers
- Population studies suggest blocking fevers relates to an increase transmission rates of associated illness
(Earn et al., 2014)
Antibiotics
Any class of organic molecule that inhibits or kills microbes by specific interactions with bacterial targets, without any consideration of the source of the particular compound or class
(Davies and Davies, 2010)
Antibiotic Resistance
the ability of microbes to resist the effects of drugs, where the germs are not killed, and their growth is not stopped
(CDC, 2017)
- World War I
- High number of infections and casualties
- Increased need to combat infection
- Treatment consisted of bandages soaked in antiseptic
(Runcie, 2015)
- Alexander Flemming
- 1928: Credited with the creation of the first antibiotics in
- Florey and Chain
- 1945: Credited with the development of
the first mass produced antibiotics
(Davies and Davies, 2010; Aminov, 2010)
- Human activities that have forced selective pressures on bacteria
- Misinformed individuals improperly handling antibiotics results in a contaminated environment
- Suceptible strains die off leaving more resistant strains to replicate
(Davies and Davies, 2010)
- Bacteria in constant contact with antibiotics are subjected to selective pressure
- Mutated bacteria become stronger and live longer
- MDR and TDR
e.g., M. Tuberculosis
- Bacteria constantly fight antibiotics in their own environment forcing resistant strains to replicate more often
(Davies and Davies, 2010)
T.gondii and Psychiatric Disorders
- Kramer and Netherlands summarized 114 cases of symptomatic toxoplasmosis
- Psychiatric disturbances were very frequent, occurring in 24 cases
- Ranged from acute psychosis to psychic alterations
- Incredibly interesting cases
- Higher suicide ideation
T.gondii and schizophrenia
- Significant studies done
- A meta-analysis done by E. Torrey, John Bartko, Zhao Lun and Robert Yolhken
- 42 identified articles
- Prevalence of antibodies to T.gondii in individuals with schizophrenia was significantly higher than the control populations
- T.gondii has also been shown to increase levels of dopamine
- Some people exhibit symptoms such as swollen glands, reduced vision or blurred vision
- Most bizarre was changes in behavior
- men are more likely to show lower superego strength,jealous,dogmatic
- women had higher superego strength, warm hearted, outgoing
- Difficulty concentrating
Parasitism
What is a parasitic relationship?
- A relationship in which one organism lives off of another organism, harming it and possibly killing it
"diseases succeed and fail in response to humanity's advances"
How can I contract T.gondii?
- rats were infected with cysts containing the parasite
- they were then put in pens with four different types of odors in four different corners; rat, human, neutral, cat and rabbit
- Results: those infected with T.gondii had no fear when faced with predator scents
Exhibit A
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071402/#ref5
https://ac-els-cdn-com.subzero.lib.uoguelph.ca/0163725882900638/1-s2.0-0163725882900638-main.pdf?_tid=fdd8124c-b374-11e7-a0c0-00000aacb362&acdnat=1508270251_d90497b8d1c32d926f6f83c026f71a20
https://ac.els-cdn.com/0162309594900027/1-s2.0-0162309594900027-main.pdf?_tid=29246904-b40c-11e7-b568-00000aacb35e&acdnat=1508335178_e44b64737490c67954ee9d972f925e36
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2001.tb03472.x/full#b2
http://www-personal.umich.edu/~nesse/Articles/Nesse-DefenseReg-EHB-2005.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944485/
http://rspb.royalsocietypublishing.org/content/281/1778/20132570.short
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703655/
References
Toxoplasma gondii
- http://www.stanleyresearch.org/patient-and-provider-resources/toxoplasmosis-schizophrenia-research/
- https://www.cdc.gov/parasites/toxoplasmosis/gen_info/faqs.html
- http://www.sciencedirect.com/science/article/pii/S0065345410410050
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1690701/pdf/11007336.pdf
- http://www.sciencedirect.com/science/article/pii/S0960982215015171
- eating undercooked, contaminated meat
- Being in contact with contaminated meat
- Drinking contaminated water
- Accidental ingestion by coming into contact with cat feces
- cleaning litter
- mother-to-child transmission
- single celled parasite
- cause of toxoplasmosis
- more thank 60 million people in the U.S are affected
- Rarely any health implications in healthy individuals
- http://www.hopkinsmedicine.org/gastroenterology_hepatology/clinical_services/advanced_endoscopy/fecal_transplantation.html
- http://embor.embopress.org/content/7/10/956
- https://microbiomejournal.biomedcentral.com/track/pdf/10.1186/s40168-016-0225-7?site=microbiomejournal.biomedcentral.com
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841828/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448690/
- https://med.nyu.edu/medicine/labs/blaserlab/v1-who_are_we.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135866/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548428/?report=printable
- https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm092810.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888801/pdf/nihms715987.pdf
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109405/pdf/fmicb-01-00134.pdf
- https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm092810.htm
Parasitic Manipulation
https://www.cdc.gov/parasites/toxoplasmosis/biology.html
- Parasites have evolved the ability to manipulate host behavior
- This ability enhances the parasites reproductive success (parasitic fitness)
- Has been documented in a few hundred host-parasite relationships
- Parasites take advantage of their hosts by altering levels of neuromodulators or neuropeptides
- Olfactory test on chimpanzee using different urine: human, leopard, lion or tiger
- Those who were infected with T.gondii approached the leopard urine more frequently than those who weren't infected