Our Microbiota: Co-Evolution and Hologenomic Theory

 

Background / Introduction

AGING: A Treatable Disease.   The unmasking of the human microbiota as our ‘second brain’, focused attention on the highest microbial concentration, the GUT, as an incredible array of 4 -5 lbs of unharnessed genetic information.  Microbial experimentation further unmasked a ‘gut brain axis” (GBA) and the importance of this information transferred both to the brain (UP) and from the brain (DOWN) to the GUT microbiota.  Cognition and Learning Disabilities could be seen in GUT and Oral changes of our microbiota, and ultimate recognition that aging could be potentially influenced by our microbial partners.   In 2017 the CDC promoted the concept that aging was a disease, potentially an infectious disease, making it a target for microbial intervention via probiotics and or antibiotics, highlighted first in the best seller “Brain Maker” (2015) and most recently (2018), “The Psychobiotic Revolution: Mood, Food and the New Science of the GUT-Microbe Connection”.  We will dissect these and the possibilities for our own health and aging, including my latest reference guide (www.globalbugs.com/Aging ).  Puppet:   Louis Pasteur.  

• Culture Plate Gang - Aging
• Aging as a Disease
• Hologenome Concept of Evolution "Dual Citizenship"
• Theories of Aging and Time, Linking: Humans, Globe, and Microbes
• Is Aging a Disease? Microbial Clock Future
• Endogenous Diseases: Microbial Clock
• Gut Microbiota and Extreme Longevity

A. Origin

National and International studies in 2007/8  unmasked the hidden microbial world of Homo sapiens and the partnering of pro-caryotes and eucaryotes,  coining the new Term “Super Organism” (Figure 1)REF 1 . Additional studies highlighted the importance of this balance in disease and health , better characterized by a phyla -signature than individual species . An “Anti-Koch “ theme emerged that recognized 6-8 Phyla versus 10,000 species in H. sapiens .  It further emphasized the genetic  strength of the pro-caryotes  (metagenomics ),  given the microbial world outnumbered the eukaryotic  1014   vs 1012 representing  8,000,000 genes vs 23,000 , respectively .

B. Development

WHAT

1.  It began with the Human Genome project (EU and US) (2007), the integration of molecular tools defining who we are, genetically (MARCO), followed shortly by who our microscopic partners are, genetically. (MICRO).(REF    ) 
2. We found our co-habitants or microbiota were more diverse and complicated than imagined, encompassing the microbial spectrum, both bacterial (16S) and recently  fungal (18S)(REF   ), with representation of potentially 10,000 species more functionally divided into 10 phyla on a taxonomy scale.  More importantly, the total number of microorganisms (10 to 12 vs 10 to 14 were essentially 200 times in greater number, representing approximately 8 million genes vs 25,000 (REF  ),providing a combined genetic pool 330 times larger than humans, which  could be envisioned as a non-structured  ‘organ system’.   
3. These findings unmasked the importance of our microbiota/mycobiota  in health and disease.  Tracking changes in the microbiota over time, particularly for chronic and metabolic diseases, allowed us to formulate a ‘Microbial Clock’ that defined time and 6-8 phylotypes in association with 10  diseases (REF   ), unmasking the significance of missing microbes with age ;   this echoing the challenge described  my Martin Blaser, MD, of diminishing microbiota with age and disease (REF  )   , a possible reflection of ONE Health: Animals, Humans and Earth.(REF    )
4. Simultaneously, the emerging, global (REF   ) use of probiotics as “therapeutic bacteria” (TB)  and Germ Therapy was astounding,  where WHO described 1/3 of population used them at an expenditure of $85 billion in 2015(REF   ).This  highlighted our terms, “dual citizenship” and “organ transplants” , catalyzing  us to provide increased education via our searchable probiotic  data base (Probiotic Solutions) (Bac-2-Health)(2013) and the use of “Partners-4-Life” Concept (www.globalbugs.org)(2016).  It also forced us to recognize the limits, perhaps consequences, of miss-used antibiotics, so eloquently described by Dr. Stewart Levy in 2002.( REF ) and the importance of “stewardship” for our microbiota as well as antibiotics (“Microbes Matter”) ;  hence, we focused our oral health and  chronic wound research with  tissue engineering   on “reconstructive microbiology”, employing the ‘disruption:reconstruction’ Hypothesis with, initially, silver followed by TB in a contour fitting gauze.(SMarT I,II, III) (Ref).
5. In 1992 (REF     ), a new description of our  beneficial synergistic relationship was introduced, Hologenomics, describing the human-microbial interaction in evolutionary terms as a central hallmark of all life on earth ; it  highlighted 3 key features (REF   ) with X characteristics (Ref ) and scientifically outlining the inter-dependence of the healthy   Holobiont upon  its total  hologenome via the combination of both Macro and Micro symbionts.  It was a parodyme shift from Pasterurs’ recognition of pathogenic bacteria, and according to   the 2011 Pulitzer award winner, Dr S Mukherjee, MD, a calling for humans to reconsider what was ‘self’ and ‘who’ we  were. It also provided an umbrella under which the manipulation of the microbial gene pool and co-evolution had credibility and a scientific hypothesis for interventional strategies with probiotics, while renewing  the need for diagnostic studies (Clinical Microbiology) in missing or shifting microbial phylotypes. (Anti- Koch)(M Blaser)
6. Hence, the timely evolution of designing, developing, and integrating a “Center (of Excellence) for Hologneomic Clinical Studies” emphasizing  probiotic as gene pools and information support,  integrating our expertise in Biofilms, Education (Partners-4-Life) (www.gloalbugs.com) and Clinical Microbiology with a  defined Mission and Goals, addressing 3 key questions.   It reflected the growing scientific interest and increased publication aligning  Hologenomics  (REF ) and co evolution with probiotics as major contributors towards better health, decreasing the use of antibiotics, while  highlighting One Health: Humans, Animals and Globe(REF).

How

HYPOTHESIS:  The use of Probiotics can in view OF Hologenomic Theory  

1. Restore/replace via Restorative Microbiology (naturally Or artificially), the historical balance via Co-evolution of Microbes and Man (Hologenomic Theory of co Evolution) and the  combined genetic strength (Hologenomics), signaling  and beneficial  interface between the two (macrobont and microbont).
2. Address with intervention the “Missing Microbiota” (M Blaser) in selected metabolic, chronic diseases from birth to death (Microbial Clock), including the aging process and associated cognitive impairment (AD).
3. Reverse the pathogenic process of selected infectious diseases associated with a microbial imbalance without the use of antibiotics (C. diff.) , recognizing evolution (patient relatives) (EnteroType I, II, III)

Why

KEY QUESTIONS/SPECIFIC AREA OF RESEACH INTEREST

1. PROBIOTICS.  What are key characteristics of ideal probiotic, including size of genome, lysogenic, biofilm producer, vs published literature.  Can we construct a chart defining a pool of studied probiotics, magnifying a construct of 3-5 probiotics, each with a known function? Can this construct recognize changes in the normal host bioburden and bring “intelligence “ to the MOA via microbial signaling. (Intelligent Design)
2. CHRONIC WOUND CARE.  Can we integrate the  SMarT Concept with the 5Es where : A)SMarT equals,  S= Synbiotic probiotic, M=Mixed probiotics, ar=minimal antibiotic resistance, T=therapy, and B)  the 5 Es:  1. Ecologically Sound (patient); 2.  Environmentally Friendly (One Health, Humans, Animals and Globe); 3.  Engineered Intelligently; 4.  Economically Feasible ( cost justifiable, downstream benefits ; 5. Education (Bac-2-Health).
3. AGING AND DEMENTIA.  Is aging a disease that is manageable with restorative microbiology, (how, when and where)??, and can dementia be altered by unmasking an early predictive change in the oral microbiota that promotes interaction with comorbidities?  Prevention and or curative.  

Linking Probiotis and the Hologenomic Theory Of Co Evolution

1. Improving a) General Health OR b) targeted diseases by making an informational change at the cellular and/ or molecular level with activity enhanced by a Prebiotic ,  together,  SYNBIOTIC,     providing co-active  libraries of genomic  information (macrobe and microbe), collectively the hologenome.
2. Microbiont’s derive their lineage from co evolution (Hologenomic Theory of Co Evolution ) together  of procaryotes and eucaryotes , recognizing  evolving   “Dual Citizenship”  and symbiosis (SYNBIOTA) and the importance  of the microbiota  acting as an  unstructured organ system with individual members assigned specific duties analogous to individual   tissue/organs, addressing potential use of  Mini (Oral/Skin )  or Maxi (Enteral) “transplants.”
3. Recasts the individual macro holobiont as subject to evolutionally  genetic forces  brought about by changes in the microbiome, including  acquisitions  of new microbes (Natural or drived, Probiotic), horizontal gene transfer (HGT), and/or changes in abundance (Ratio) within the macrobe (host), and transferable to offspring.
4. Recognize the importance of “Missing Microbes “, a declining information library (microgenome) over time (M Blaser), often focused in targeted metabolic diseases (chronic) in our  Microbioal Clock and the potential of Replacement Therapy or Restorative Microbiology (probiotics), recognizing “loss of  microbial diversity”,(particularly low frequency background isolates) may directly contribute to pathogen selection and persistence (VAP).
5. Emphasize the importance of recognizing “who we are” as a individuals  (macrobe and microbe  holobiont’s)(S Mukherjee) and the  CENTRISTS  feature of the latter  as  Partners in Life, short and long, health and disease,  possibly aging,  acting as a “declining  biomedical network” or intergenomic association, potentially amenable to probotics.

Mission

1. MEDICINE.  Explore and expand the medical/dental benefits of probiotic intervention (GERM THERAPY as disarm and replace) as genetic resources (Gene Mining or Functional Genomics), recognizing the co-evolution (Shared Benefits or “mutualism”) of both human and microbial symbionts and the consequences to the total hologenome (Macro and Micro) in health and disease.
2. EDUCATION.  Provide for the public and professional health care provider, a searchable library of information on probiotics and the strengths and merits of individual research studies (Bac-2-Health)
3. MICROBILOGY.  Unmask the changing Microbial Clock and it phylotypes in chronic and infectious diseases, addressing a diminishing/missing microbiota and its impact as potential targets for probiotic intervention (RESTORATIVE MICROBIOLOGY) in diseases such dementia and aging and local, including  chronic wound care and VAP.
4. RESEARCH. Define the key characteristics of beneficial probiotics, and clarify/define  the pathways (Ying/Yang Hypothesis) that microbes interact with humans, recognizing the gut brain axial  and that probiotics can be immune modulators and/or bioburden reducers, the overall  consequence to health or disease organized as pro-inflammatory vs healing, best described by the Yin/Yang Hypothesis.    

C. Intervention

In 2013, we introduced our 4 stage color-coded Microbial Clock (MC); this addressed published microbial phylotype  changes to 2 parallel diseases (2015):  1)young ( Asthma and Autism )   and old ( VAP and AD ); this was followed (2016) by  tracking oral microbiota changes in patients with cognitive impairment, reporting  3)missing microbiota, all highlighted by 4) potential  intervention  of restorative microbiology (probiotics), grouped   in our educational,  searchable data base. (2016) (Probiotic Solutions, www.globalbugs.com)

• Aging and Intervention Incorporating AI
• Interactive Web-Based Probiotics Database Public and Healthcare Professionals
• Gut and Brain Axis
• Aging and Probiotics: Cross Section of Published Articles
• Microbial Clock: Composite Disease Signature in Aging

D. Calculating Your Microbial Credit Score

Introduction

Teaching microbiology to aged learners (“aged”, >55yo) can be a difficult task given the unfamiliar content.  Recently, this has been exacerbated via the weaponization of public health, necessitating the accurate education of this voting population; they will elect decision makers on their health programs when it counts most: retirement.

Goals/Purpose

Recognizing the dynamics of an aging population (FIG I), we wanted to track aged participation in voting, recognizing electorate naivete in science; this also acted as a catalyst for expanding  microbial education using a successful template that highlighted “a banking theme.” (FIG IA) (REF 1)  Its purpose was to provide a common tool to measure microbial health over a lifetime: the Microbial Credit Score (MCS); it could track health decision affecting the human microbiota.

Methods

We used US data for 5 recent presidential elections, 2000-2020, emphasizing voter registration and participation for the aged (FIG 2).  The creation of the MCS to educate the aged via “banking”, was discussed with a bank manager, bank credit manager, and bank risk manager. All supported the FICO Financial Credit Score model with financial points as a comparative template for our Microbial Credit Score. (FIG III)

Results

The US population is aging, and characterized by an increase in voter registration and voting since 2000: up 17%. (FIG II) The Microbial Credit Score model was arbitrarily divided into 3 Sections, color coded from Green to Yellow/Orange, to Red, top to bottom; this corresponded to 850-750 pts., Good, 739-580 pts.  Fair, and 579 -300 pts., Bad, with 660 deemed Neutral 9FIG IV).   For both the Financial Bank and the Microbial Bank, we compared parallel growth curves from 25-65 yr., “Accumulation”, and 66-90 yr., “Protection” (FIG V), highlighting 3 ‘Wealth Disruptive Categories’, each with 5 ranked, scored ‘Impact Values’ of +30, 0, and-30 pts. (FIG VI) These included ‘Behavioral Categories’, but emphasized previous hospitalization, antibiotics, nursing home, dental care, and co-morbidities, where applicable.   Ultimately, parallel Summary Plots were created for Financial and Microbial activity, at 6-time intervals, separated by 15 years from “Accumulation” to “Protection” as X(Score) vs Y(Time), a Microbial Histogram; Neutral score was 660pts for FICO and MCS, the start for score calculations. (FIG VII)  

Conclusion

Our ‘Banking Theme’ as an educational tool continues to expand, providing an understandable base for aged individuals not comfortable with science and at risk of misinformation.  Here, we introduced a MCS, providing an active tool to compare their own microbial health to financial, using a recognized score: Good, Fair, Poor. 

Calculate your own Microbial Credit Score.