The document discusses the impact of gut microbiota and lifestyle on health, emphasizing the importance of diet as medicine, as referenced by historical figures like Hippocrates and Maimonides. It highlights the connection between chronic inflammation, autoimmune diseases, and factors such as vitamin D and microbiome diversity, noting that a healthy lifestyle can mitigate many conditions traditionally treated with medication. The need for revised understandings in medicine is emphasized, particularly concerning the roles of diet, probiotics, and the epigenetic interactions between environment, microbiome, and genetic expression.

1. Dr. Fathi Neana, MD
Chief of Orthopaedics
Dr. Fakhry & Dr. A. Al-Garzaie Hospital
March, 13 - 2019

3. Gut Microbiota for Health
World Summit March 23-24, 2019

4. Tomorrow's Medicine

5. "Let thy food be thy medicine and thy medicine be thy food"
Hippocrates 460 BC - 370 BC
"No illness which can be treated by diet should be treated by any
other means”
Moses Maimonides, the great
12th century physician
Tomorrow's Medicine
‫يقول‬ ‫وسلم‬ ‫عليه‬ ‫هللا‬ ‫صلى‬ ‫هللا‬ ‫رسول‬،‫صلبه‬ ‫يقمن‬ ‫أكالت‬ ‫آدم‬ ‫ابن‬ ‫بحسب‬ ،‫بطن‬ ‫من‬ ‫شرا‬ ‫وعاء‬ ‫آدمي‬ ‫مأل‬ ‫ما‬
‫لنفسه‬ ‫وثلث‬ ‫لشرابه‬ ‫وثلث‬ ‫لطعامه‬ ‫فثلث‬ ‫محالة‬ ‫ال‬ ‫كان‬ ‫فإن‬.
‫رواه‬‫الترمذي‬‫وصححه‬‫األلباني‬
Messenger of Allah ( ‫ﷺ‬) say: "No man fills a container worse than his stomach. A
few morsels that keep his back upright are sufficient for him. If he has to, then
he should keep one-third for food, one-third for drink and one-third for his
breathing.“ [At-Tirmidhi].
‫هللا‬ ‫صلى‬ ‫هللا‬ ‫رسول‬
‫وسلم‬ ‫عليه‬

6. Do not treat food with medicine, Let the food be the medicine,
and the Medicine be the food
Dr. Sarah Hallberg May 4, 2015
What are the gut microbiota and human microbiome?
By Markus MacGill - Reviewed by Saurabh (Seth) Sethi, MD
MPH
Last updated Tue 26 June 2018
Let thy food be thy medicine….when possible
Renger F. Witkamp Klaskevan Norren
European Journal of Pharmacology Volume 836,
5 October 2018, Pages 102-114
Tomorrow's Medicine

7. Lifestyle diseases can be
cured
By Therapeutic lifestyle
Rather than treating risk
factors by drugs for life
Manifestations
Vs.
Root cause
1- Chronic inflammation
2- Mitochondria dysfunction
Life style
Underling risk factors
Healthy diet
Omega 6-Sugar
Regular
Exercise
Our current
understandings
should be revised
Prescription drugs is the
Third leading cause of death
in U.S. after heart diseases
& cancer

8. Potential role of probiotics in the management of gastric ulcer (Review) Article in Experimental and therapeutic medicine · April
2016 DOI: 10.3892/etm.2016.3293 CITATIONS 3
Peptic ulcer disease including both gastric and
duodenal ulcer (Hyper vs. Hypoacidity)
1- decades of preference for surgical interventions in the form of
gastric resections, vagotomy etc.,
2- The concept of acid in peptic ulcer disease, which was the basis of
treatment of peptic ulcer was revolutionized by the discovery of H2-
receptor antagonists and PPI (proton pump inhibitor)
3- After the discovery of Helicobacter pylori organism as the
causative factor a triple drug regime further modified to sequential
therapy to avoid antibiotic resistance.
4- Now the over growth of H pylori is considered as a sort of
Dysbiosis or SIBO. The Role of probiotics & intermittent fasting
5- This recognition has not concluded the chapter on peptic ulcers.
The mainstream medical care is
changeable
Our current understandings should be revised

9. Dysbiosis and SIBO
H. Pylori
Candida

10. VDR wide range of biological actions
which is critical for all body systems
including the bones, nerves, proper
growth, mineral metabolism, muscle
tone, insulin production, fertility, etc
Therefore now seen as an important
nutrient in preventing many chronic
diseases
Vitamin D is a Steroid Hormone
A Ligand for VDR (Vitamin D nuclear Receptor)
– Vit D nuclear receptors (VDR) found in most tissues and cells in the
body
– Wide range of biological actions
– Regulate the immune System
1- VDR is present in most immune cell types, particularly in antigen-presenting cells (APCs) such as
monocytes, macrophages and dendritic cells
2- VDR to express antimicrobial peptides (AMPs) such as cathelicidin and beta defensins which attack
pathogens
3- In general, the innate immune system is enhanced and the adaptive immune system is inhibited by
1,25(OH)2D
– Regulate the Microbiota
– Great rule in autoimmune disorders
– Inhibits cellular proliferation induce terminal differentiation
– Inhibits tumor angiogenesis
– Inhibits rennin production
– Adequate vitamin D in macrophages an Adaptive immunosuppressive
agent.
– Stimulate insulin production
– Allows for effective communication between cells
– Helps to maintain a healthy calcium concentration in the cells
– Stimulate production of compounds that kill bacteria by stimulates
its own destruction (Apoptosis)
The mainstream medical care is changeable
Our current understanding of the factors leading to chronic inflammation
should be revised after the recent researches on vitamin D

11. The innate and adaptive
immune systems

12. Ubiquitin and immune system modulation Cells of both the innate and adaptive arms of the immune
system are crucial for immune reactivity and self‐tolerance.
Defects in the expression of E3 ligases or DUBs can lead to deregulation of these processes which can
resulting in auto immunity or auto inflammation.
1- Autoimmune disorders
are characterised by disturbed function of mTEC and DCs (impairment in their presentation of
self‐peptides to T cells; highlighted in red) or by perturbed peripheral tolerance, which will lead to the
development of self‐reactive T and/or B cells (highlighted in red), production of autoantibodies and
subsequent tissue destruction.
2- During autoinflammation,
the innate immune cells are hyperactive (highlighted in red) and release pro‐inflammatory cytokines,
including IL‐1β and TNF, which will result in the development of auto‐reactive inflammation.
Auto inflammation
Insulin resistance
Metabolic syndrome
Auto immunity
Auto immune disorders
>100 AID
Insulin
Ligand
Calcitriol
Ligand
INR
VDR

13. Initial symptoms are often intermittent and unspecific until the disease becomes acute.
Medical education provides minimal learning about autoimmune disease.
Specialists are generally unaware of interrelationships among the different autoimmune diseases.
Research is generally disease-specific and limited in scope. More information-sharing and crossover
among research projects on different autoimmune diseases is needed.
According to the American Autoimmune Related
Disorders Association (AARDA)
An estimated 50 million Americans suffer with
autoimmune disease (AID)
compared to 9 million with cancer and 22
million with heart disease.
AID is the #1 cause of death in women under
the age of 65
There are more than 100 forms of AID currently
recognized by research.
Symptoms cross many specialties and can
affect all body organs.

14. The three most well recognized mechanisms :
1- Excessive hygiene
"microbiome depletion theory
2- Molecular mimicry
3- Intestinal permeability (Leaky Gut)
There are 5 causes that trigger the three mechanisms above:
1- Food (especially gluten)
2- Chemical exposures (including things like pesticides,
vaccines and other medicines)
3- Infections and microbiome imbalances (Dysbiosis)
4- Nutritional deficiencies – vitamins and minerals
5- Chronic or severe acute stress events
What Are The Mechanisms That
Trigger Autoimmune Disease?
All three of these issues can lead to chronic inflammation. It is the chronic
inflammation that medicines try to target.
But the bigger questions to ask are – What causes autoimmune disease,
and what activates these three mechanisms?
Dr. Peter Osborne has served as the
executive director and the
vice president for the American
Clinical Board of Nutrition. He is on
the advisory board for Functional
Medicine University. He has been
featured on Fox News, CBS,
Celiac.com, The Gluten Summit, and
The People's Pharmacy Radio. He is
one of the
world's leading authorities on gluten
sensitivity, and ... The Journal of
Gluten Sensitivity, and many
other nationally
recognized publications.
Videos

15. Vitamin (Hormone) D metabolism
1- Precursors 2- ligand (1,25(OH)2-D3) 3- Receptor VDR
1
2
3
VDR: Vitamin D receptor
RXR:Retinoid X receptor

16. The VDR transcribes over 1,400 genes
which accounts for 4% of all human
genes
1,400 genes are no longer able to be
transcribed when the VDR is
deactivated.
VDR deactivation down regulate the
innate immunity and up regulate the
adaptive immunity (Maladaptation ->>
Autoimmunity)
Vitamin D Nuclear receptor (VDR)
Regulate the immune System and the Microbiota

17. Auto immunity simplified explanation
Microbiota Dysbiosis
Leaky gut
VDR deactivation
Ligand from pathogens
Innate immunity
Down regulation
Resistant pathogens
chronic illness
Adaptive immunity
Up regulation
Chronic inflammation
Antibodies formation
Auto immune disorders
Metagenome
Varies chronic diseases
symptomology including

18. The Ligand:
1,25-dihydroxy vitamin-D
(calcitriol)
The Receptor
VDR deactivation
(? Increased 1,25-dihydroxy
vitamin-D (calcitriol) -
no breakdown
Innate immunity down regulation
VDR agonist Olmesartan
Root cause of VDR Deactivation
Ex : Pathogens (dysbiosis – leaky gut)
Global Look for Causes of vitamin D deficient function
Causes may be interrelated
Calcitriol
Calcitriol
Ligand
VDR
VDR
Mal adaptive immunity (autoimmunity)
Treatment of AID manifestations1-Insufficient vitamin D
precursors
2- Severe liver or kidney
disease
Root cause
Factors that
Deactivate VDR
Ex : Pathogens
(Dysbiosis –
Leaky gut)

19. Microbiota
Dysbiosis

21. Diversity and Biodiversity
Biological diversity, or biodiversity,
is the scientific term for the variety
and variability of life on Earth.
Every living thing, including man
is involved in these complex
networks of interdependent
relationships, which are called
ecosystems.
Biodiversity
is the key indicator of the
health of an ecosystem.

22. How killing wolves to protect livestock may backfire
BY SARAH ZIELINSKI
12:25PM, MARCH 2, 2016
Lone wolves are more likely to go after goats and other livestock than wolves
living in packs. – increase in pairs

23. Counting the costs of Vulture decline – an appraisal of human
health and other benefits of Vultures in India
Article (PDF Available) in Ecological Economics 67(2):194-
204 · September 2008 with 1,402 Reads
Diclofenac in veterinary use

24. Extinction of Vultures led to over growth of rodents
Rodent outbreaks in North America Gary W. Witmer USDA-APHIS-Wildlife
Services, gary.w.witmer@aphis.usda.gov
August 2004 Rodent Ecology and Plague in North America Gary W. Witmer USDA-APHIS-
Wildlife Services, gary.w.witmer@aphis.usda.g

25. U.S. DEPARTMENT OF AGRICULTURE
Fire ants and Phorid flies as Biocontrol Agents
Last Modified: 10/4/2017

26. In 1958 Mao Zedong ordered all the
sparrows to be killed because they ate
too much grain
It was noticed that insect infestation of
crop fields had soared.
Sparrows ate pests such as locusts
After the campaign, the locusts lost
their major predator.
This meant that killing the sparrows
was counter-productive
The sparrows, it seemed, didn’t only
eat grain seeds. They also ate insects.
The worst environmental disasters in history
45 million people died in a famine

27. 10 Most dangerous antibiotic-resistant bacteria
E Coli resistant to Quinolones
due to abuse of Quinolones in veterinary care

28. ٍ‫ْض‬‫ع‬َ‫ب‬ِ‫ب‬ ‫ُم‬‫ه‬َ‫ض‬ْ‫ع‬َ‫ب‬ َ‫اس‬‫ه‬‫ن‬‫ال‬ ِ ‫ه‬‫اَّلل‬ ُ‫ع‬ْ‫َف‬‫د‬ َ‫وَل‬َ‫ل‬َ‫و‬ُ‫ض‬ْ‫ر‬َ ْ‫اْل‬ ِ‫ت‬َ‫د‬َ‫س‬َ‫ف‬‫ه‬‫ل‬ِ‫ك‬ََٰ‫ل‬َ‫و‬‫ى‬َ‫ل‬َ‫ع‬ ٍ‫ل‬ْ‫ض‬َ‫ف‬ ‫و‬ُ‫ذ‬ َ ‫ه‬‫اَّلل‬ ‫ه‬‫ن‬َ‫ين‬ِ‫م‬َ‫ل‬‫ا‬َ‫ع‬ْ‫ال‬(251)‫ا‬ ‫سورة‬‫لبقرة‬
And if Allah had not repelled some men by others the earth would have been corrupted.
But Allah is a Lord of Kindness to (His) creatures.
Sura Al-Baqara: Verse 25
ِ‫ض‬ْ‫ر‬َ ْ‫اْل‬َ‫و‬ ِ‫ت‬‫ا‬َ‫او‬َ‫م‬‫ه‬‫س‬‫ال‬ ُ‫ق‬ْ‫ل‬َ‫خ‬ ِ‫ه‬ِ‫ت‬‫ا‬َ‫ي‬‫آ‬ ْ‫ن‬ِ‫وم‬ِ‫ن‬‫ا‬َ‫و‬ْ‫ل‬َ‫أ‬َ‫و‬ ْ‫م‬ُ‫ك‬ِ‫ت‬َ‫ن‬ِ‫س‬ْ‫ل‬َ‫أ‬ ُ‫ف‬ َ‫َل‬ِ‫ت‬ْ‫اخ‬َ‫و‬ْ‫م‬ُ‫ك‬ٍ‫ت‬‫ا‬َ‫ي‬ ََ ََِ‫ل‬ََٰ‫ذ‬ ِ‫ف‬ ‫ه‬َّ َِِ‫ين‬ِ‫م‬ِ‫ل‬‫ا‬َ‫ع‬ْ‫ل‬ِ‫ل‬(22.)‫سورة‬
‫الروم‬
And among His Signs is the creation of the heavens and the earth, and the variations in
your languages and your colours: verily in that are Signs for those who know.
Ar-Room: Verse 22
Diversity and Bio Diversity is a rule
that govern our life on earth

29. Diversity and Biodiversity
Like all healthy ecosystems,
Richness of microbiota species characterizes
the GI microbiome in healthy individuals.
Conversely, a loss in species diversity is a
common finding in several disease states.
Microbiota Biodiversity helps us:
1- Combat aggressions from other
microorganisms,
2- Maintaining the wholeness of the intestinal
mucosa.
3- Plays an important role in the immune system,
4- Performing a barrier effect.
5- A healthy and balanced gut microbiota is key to
ensuring proper digestive functioning.

31. Environment
Epigenome Microbiome
Life
Consciousness-Spirit
Internal environmental
External environmental
Record of the chemical changes
to the DNA and histone
Epigenetics, Gut microbiome and the Environment, a sensitive interplay

32. How epigenetics, our gut microbiome
and the environment interact to change our lives
Ben Locwin | Genetic Literacy Project | October 17, 2016
Research presented at the American Association for the Advancement of
Science 2014 conference
1- Supported that epigenetics and some form of heritability are in fact
linked.
2- Much of our lives and life trajectories could, in fact, reflect a sensitive
interplay between our environment, genes (epigenetics) and microbiome
3- The intersection of all of these factors is, quite simply, ‘us.’ as in the Venn
diagram
1- Children raised in more rural areas (more exposure to animals, dirt, debris, molds, pollen, etc.) suffer from
fewer cases of allergies than those children raised in more urban settings. Again, that pattern suggests an
interplay of our external environment, microbiome, and epigenetics.
2- Some novel research indicates that certain compounds produced by certain gut flora can make colon
cancer more prevalent by blocking the activity of DNA repair proteins.
3- The composition of the gut microflora can be changed very ‘rapidly and reproducibly’ in response to dietary
changes. Some of the consequences are directly due to microbial gene expression.
4- The inflammatory cascade of Crohn’s disease seems to be related to the gut microbiome and specific
microbes in particular.

33. An epigenome consists of a record of
the chemical changes to the DNA and
histone proteins of an organism
These changes can be passed down to
an organism's offspring via
transgenerational epigenetic
inheritance.
Wikipedia
1- The epigenome is highly sensitive
to external environmental factors in early life,
such as nutrition, stress, endocrine disruption
and pollution
Epigenetics, Gut microbiome and the Environment
a sensitive interplay
2- The epigenome is highly sensitive to internal environmental (Microbiota)
3- The changes in the epigenome can induce long-term changes in gene expression and phenotype.
4- The external environmental factors (our environment) affects our microbiome (The internal
environmental)

34. Epigenetics and lifestyle
Jorge Alejandro Alegría-Torres,1 Andrea Baccarelli,2 and Valentina Bollati3,*
Epigenomics. Author manuscript; available in PMC 2013 Aug 26.
Published in final edited form as: Epigenomics. 2011 Jun; 3(3): 267–277.
doi: 10.2217/epi.11.22 PMCID: PMC3752894 NIHMSID: NIHMS498542 PMID: 22122337
The concept of “lifestyle” includes different factors such as nutrition, behavior, stress,
physical activity, working habits, smoking and alcohol consumption.
Increasing evidence shows that environmental and lifestyle factors may
influence epigenetic mechanisms, such as DNA methylation, histone
acetylation and microRNA expression.
Several lifestyle factors have been identified that might modify epigenetic patterns,
such as diet, obesity, physical activity, tobacco smoking, alcohol consumption,
environmental pollutants, psychological stress, and working on night shifts.
Most studies conducted so far have been centered on DNA methylation, whereas only a
few investigations have studied lifestyle factors in relation to histone modifications and
miRNAs.
Current evidence indicating that lifestyle factors might affect human health
via epigenetic mechanisms.

35. Wi-Fi - EMFs
Disruption of the VGCC.
Leaky Barriers
leaky gut
How Cell Phones and Wireless Routers Mess Up Your Gut
July 11, 2016 Rob EMF, Microbiome, Research
Microbiota
Dysbiosis
VDR deactivation
Ligand from pathogens
1400 genes out of order
Innate immunity
Down regulation
Resistant pathogens
chronic illness
Adaptive immunity
Up regulation
Chronic inflammation
Antibodies formation
Auto immune disorders
Example to show how the causes of Lifestyle diseases are
interrelated
Western lifestyle
stress, a hyper-hygienic lifestyle ,deworming
treatments at an early age, chlorinated water,
excessive antibiotic treatments, Western diet
low in fiber and high in carbs, toxins, drugs.

36. Microbiota – the forgotten organ

37. The gut microbiota is with humans from birth and affects function throughout the body.
The human body is a host to 10 - 100 trillion microbes in a symbiotic relationship.
They outnumber the human cells in the body 10 to 1.
This benefits both the microbes and their hosts, as long as the body is in a healthy
state
The human microbiota consists of a wide variety of bacteria, viruses, fungi, and other
single-celled animals that live in the body.
Over 1000 different species of microorganism making up the human microbiota.
The microbiome is the name given to all of the genes inside these microbial cells
(metagenome).
Microbiota the forgotten
organ
What are the gut microbiota and human microbiome?
By Markus MacGill - Reviewed by Saurabh (Seth) Sethi, MD MPH
Last updated Tue 26 June 2018

38. The microorganisms living inside the gastrointestinal tract amount to around
4 pounds of biomass. Every individual has a unique mix of species.
The microbiota is important for nutrition, immunity, and effects on the brain
and behavior.
It is implicated in a number of diseases that cause a disturbance in the normal
balance of microbes.
The biggest populations of microbes reside
in the gut. Other popular habitats include the
skin and genitals.
The microbial cells and their genetic material, the
microbiome, live with humans from birth. This
relationship is vital to normal health.

39. Microbiota – the forgotten organ
The Gut Microbiota
Complex community of microbes estimated to contain:
1- 200 trillion cells
2- > 1000 diverse microbial species
3- 10 times the number of human cells in our body
4- Gut Microbiome is 150 times larger than the human
genome
5- 100 to 1,000 times more DNA than ours!!!
6- 20,000 functions & make 100’s of thousands of
biochemicals
7- Genes for making hormones, enzymes, etc. (Humans =
23,000 - Microbes = 4.5 million)
8- Found even in “sterile” zones (e.g. lungs & womb)

40. 1- Prevents colonization by pathogens
2- “Educates and Modulate the immune
system” Immunomodulatory cell signaling
3- Epigenomic expression e.g., butyrate
and histone deacetylase inhibition
4- Metabolic role
- Digestion-caloric extraction
- Produces
• SCFA short chain fatty acids
(hypertension)
• Gut hormones/permeability
• Vitamin modification Vit K and folate
5- Participates in drug metabolism
• Activates 5-ASA 5-amino-salicylic
acid (colorectal cancer protection)
6- Deconjugates bile acids – Detoxification
7- Cytokine modulation – insulin/leptin
8- 99% genome from microbes
9- Neurotransmitters - Talk to the vagus
nerve
Gut Microbiota
Functions

41. Dysbiosis is any perturbation of the normal microbiome content that could disrupt
the symbiotic relationship between the host and associated microbes,
a disruption that can result in diseases, such as inflammatory bowel disease and
other gastrointestinal (GI) disorders, including gastritis, peptic ulcer disease,
irritable bowel syndrome, and even gastric and colon cancer [3–6].
From: The Microbiota in Gastrointestinal Pathophysiology, 2017
Dysbiosis
Microbial Imbalance Inside the Body
Types of Dysbiosis are:
1) Loss of beneficial bacteria
2) Overgrowth of potentially
pathogenic bacteria
3) Loss of overall bacterial
diversity

43. A gut out of balance means a body out
of balance which means illness
• Inflammation
• Allergies
• Infections
• Nutrient deficiencies
• Weight Gain
• Asthma-allergies – Autoimmunity
• Arthritis
• Metabolic Bone disease
• Skin problems e.g. eczema, rosacea
• Mood disorders - Cognitive decline-
Alzheimer's
• Cancer

45. A gut out of balance means a body out of balance
which means illness
Gut Dysbiosis may contribute to psoriatic arthritis by
overgrowth of inflammatory strains of bacteria and
yeasts, by reduction of tolerogenic strains including F.
prausnitzii , or by a combination of both
Source publication

48. Dysbiosis, SIBO, Increased Intestinal Permeability (leaky gut)
Obesity – Diabetes – Cardiovascular risk – Cancer - etc
Abbreviations:
(TLR4) Toll-like receptor 4
(LPS) Lipopolysaccharide
(SAT) Subcutaneous adipose tissue
(VAT) visceral adipose tissue
(PGC-1α) Peroxisome proliferator-activated receptor gamma
coactivator 1-alpha is a protein ... a key regulator of energy
metabolism
(FIAF) Fasting-Induced Adipose Factor or ANGPTL4, a protein that
inhibits (LPL)
(LPL) lipoprotein lipase
(SCFAs) Short chain fatty acids
(NNS) Non nutritious sweetener
(SIBO) small intestinal bacterial overgrowth
(NASH) Nonalcoholic steatohepatitis
(FFA) free fatty acids

49. Figure 1. Speculated health implications of gut microbiota. NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic
steatohepatitis; HS, hepatic steatosis; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; UC, ulcerative colitis.

50. Vitamin D deficient function
(ligand – Receptor VDR)
Western life style
Antibiotics
Steroids
Birth control pills
Other Drugs, NSAID -Aspirin
Stress
Poor Diet sugar – processed
Infections
Diseases
Bottle Feeding
Old Age Extreme age
Immune suppression
Pollution
Radiation EMFs
Alcohol
Toxic Chemicals
Poor dental hygiene
Dental Work (mercury)
What can alter or damage
Gut Flora
Causes of Dysbiosis

51. Example: Bacterial
Dysbiosis
Understanding Peptic Ulcers, H. Pylori and the Connection to Gut Dysbiosis
OCTOBER 4TH, 2018
Peptic Ulcers, H.Pylori and the Link to Gut Dysbiosis | Bio-K+
https://www.biokplus.com/.../understanding-peptic-ulcers-h-pylori-and-the-connection-t...

52. Western lifestyle factors
that lead to autoimmunity
diseases
The figure represents the main factors that
contribute to the disruption of gut
homeostasis and rise in autoimmune
diseases in Western countries, such as
stress, a hyper-hygienic lifestyle that
includes deworming treatments at an early
age, drinking chlorinated water (19), and
excessive antibiotic treatments (34), the
Western diet which is characteristically low
in fiber and high in saturated fat (35), toxins
(36), drugs (36-38), and vitamin D
deficiency (39).
Furthermore, Vitamin D deficiency and
vitamin D receptor function have also been
shown to disrupt gut homeostasis and
consequently immune tolerance (40, 41).
All of these factors can lead to intestinal
Dysbiosis, more susceptibility to pathogenic
infections and intestinal permeability, which
predispose to lipopolysaccharides
translocation and trigger inflammatory
immune responses such as TNF-α and
IFN-γ (42). The loss of immune
homeostasis can lead to food intolerances
and allergies, which can subsequently lead
to autoimmune disease development (19).

53. The Fungal Mycobiome
and Its Interaction with Gut Bacteria in the Host
Qi Hui Sam,1 Matthew Wook Chang,2,3 and Louis Yi Ann Chai1,4,*
Patrick C. Y. Woo, Academic Editor Int J Mol Sci. 2017 Feb; 18(2): 330. Published online 2017 Feb 4. doi: 10.3390/ijms18020330
PMCID: PMC5343866 - PMID: 28165395
Figure 1. The multifaceted factors influencing gut microbiome and mycobiome interaction.

54. DNA sequencing
Solved the problem of negative cultures
The interaction between the mycobiome and microbiome
It includes any method or technology that is used to determine
the order of the four nitrogenous bases: adenine,
guanine, cytosine, and thymine. (AGCT)
The advent of rapid DNA sequencing methods has greatly
accelerated biological and medical research and discovery.
The advent of sequencing technology has endowed us with the capacity to study
microbes constituting the human commensal community that were previously
non-culturable. Much of the initial works have concentrated on the bacterial flora
constituting the gut microbiome, since specimens are readily accessible in health and
disease. Less, however, is understood of the “silent population”—the fungal
species, also known as the mycobiome. Living in symbiosis with bacteria as
commensals in our body, it is perceivable that the mycobiome exerts an inadvertent
influence on the microbiome. We review here the recent knowledge gained from study of
the interaction between the mycobiome and microbiome in health and disease
susceptibility, immunity, and consequences from antimicrobial

55. Example: Fungal
Dysbiosis

56. Systemic Candidiasis
The most common causes of increased risk for candida
overgrowth include:
•Immuno compromised (for example, people who have had an
organ transplant, have HIV/AIDS, or are on cancer chemotherapy)
•Medications such as broad-spectrum antibiotics
•High stress lifestyle
•Oral contraceptives
•Dietary : refined sugars and carbohydrates
•Cancer treatments
•Oral corticosteroids
•Intensive care unit (ICU) patients
•People who have had surgery,
especially gastrointestinal surgery
•People who have a central venous catheter
•Very low-birth-weight infants
•Extreme age
•People who have a very low neutrophil (a type of white blood
cell) count (neutropenia)
•People who have kidney failure or are on hemodialysis
•People who have diabetes

57. Systemic candidiasis includes a spectrum of yeast
infections caused by different species (types)
of Candida
It is a serious infection that can affect the blood,
heart, brain, eyes, bones, or other parts of the body
Although there are over 200 species of Candida, five
different species of Candida cause 90% of systemic
candidiasisl:
The most common form of this invasive yeast
infection is when Candida enters the bloodstream
(candidemia).
Systemic candidiasis is the most common fungal
infection among hospitalized people in high-income
countries, including the United States.
Diagnosis can be difficult, especially when
the Candida is not found in the bloodstream
Treatment usually includes oral or intravenous (IV)
antifungal medications
Last updated: 12/15/2016
Systemic Candidiasis

58. Systemic Candidiasis
SIGNS OF CANDIDEMIA INCLUDE:
1- Fever and chills that do not improve with
antibiotics.
2- Can cause Septic shock
(low blood pressure, fast heart rate, and
rapid breathing)
3- Depend on the organ or system which is
infected.
central nervous system (brain and spinal
cord), abdomen, heart, kidneys, liver,
bones, muscles, joints, spleen, and/or
eyes.
Candidemia may be present, but not in all
cases.

59. Effectively treating Candida involves
1- stopping the overgrowth,
2- restoring the friendly bacteria that usually keep them
in check,
3- repairing your gut so that Candida can no longer
enter your bloodstream.
I accomplish this with a simple and proven three-wave attack in
my 30-day Candida Breakthrough® Program. The steps are as
follows:
•Step 1: First, you need to starve the Candida by removing the
foods that feed it from your diet. This means cutting
all sugar and alcohol, and limiting carbohydrates such as fruit,
starchy vegetables, grains, and legumes.
•Step 2: Next, you’ll want to attack the Candida by taking
supplements that destroy Candida’s cell walls. I like to use
Candifense™ as well as Caprylic Acid, both of which are
excellent at breaking down the walls of Candida cells.
•Step 3: Finally, you will repopulate your gut with good bacteria
using a high-potency probiotic to keep Candida under control.
While battling Candida, I recommend a probiotic supplement
containing 100 billion colony-forming units (CFUs) to restore
your gut’s healthy microbial balance.
How do you treat Candida overgrowth?

60. Management
Of Dysbiosis

61. Management of Dysbiosis
lifestyle interventions to restore balance and health to the gut
microbiome

62. Short-term intermittent fasting prevent gut pathologies, improves gut health and extends
lifespan in fruit flies independent of the TOR pathway[viii].
Fasting for 24-hours either every other day or twice a week extends the lifespan in rodents
by up to 30%[ix]
Intermittent fasting promotes clearance of pathogens and infectious bacteria and helps to
heal the gut in mice infected with salmonella[x]
Fasting lowers overall inflammation in the body which causes oxidative stress, DNA damage,
and promote disease
Fasting protects the gut against the negative effects of stress[xi], which promotes
inflammation and cause damage to the intestinal walls. Fasting activates a pathway called cAMP,
which further activates genes that promote intestinal lining integrity and strength[xii]. The cognitive
benefits of fasting on the brain will also improve your mood and improve stress resiliency which
protects against leaky gut again. agy[xviii].
Intermittent Fasting and Gut Health
September 26, 2018 Siim Land
How fasting affects the gut microbiome and your overall health
Intermittent fasting promotes white adipose tissue browning and reduces obesity by shaping the gut microbiome[xiii].
The gut microbiota influences adipose tissue browning and insulin sensitivity[xiv] by signaling the browning of white fat into brown
fat[xv].
Caloric restriction and weight loss increase the number of beneficial bacteria in the gut called Bacteroidetes[xvi]. Obese
people have less of these bacteria than lean people. Caloric restriction enriches phylotypes in the gut that are positively correlated
with increased lifespan[xvii]
The benefits of fasting on gut are derived from not just the direct impact on the microbiome but also
because of increased insulin sensitivity, reduced inflammation, stronger immune system, and removal
of dysfunctional cells through autophagy

63. What causes alterations of the human microbiome
• Dietary changes : e.g. refined, processed
simple starches and sugars “carbohydrate-
dense” foods
• Marked decreases in fermentable fiber
• Antibiotic use: in prescriptions and in
industrialized foods
• Glyphosate: as broad-spectrum systemic
herbicide . It is applied to the leaves of plants to
kill both broadleaf plants and grasses.
Glyphosate is organophosphorus compound
used to regulate plant growth and ripen
fruit. Glyphosate was first registered for use in
the U.S. in 1974.
• Hygiene hypothesis
• Prior GI infections; H. pylori; systemic
infections SIBO-small intestinal bacterial
overgrowth
• Medications: e.g. PPIs, steroids,
chemotherapy

64. 1- To address dietary and lifestyle
issues, and to begin the process of
dietary education and change.
2- To normalize digestion and
absorption.
3- To normalize the balance of
gastrointestinal bacteria.
4- To promote a balanced system of
detoxification.
5- To promote gastrointestinal healing.
5-R Program
Goal for digestive health is to accomplish the following

65. 1- Remove:
Remove GIT stressors: allergic foods, parasites or other bad bugs
such as bacteria or yeast.
using an allergy “elimination diet” or taking drugs or herbs to eradicate a
particular bug.
2- Replace:
Replace digestive secretions: digestive enzymes, hydrochloric acid and
bile acids that are required for proper digestion and that may be
compromised by diet, drugs, diseases, aging, or other factors.
3- Reinoculate:
Beneficial bacteria flourish by taking probiotic foods or supplements that
contain the so-called “good” bacteria such
as bifidobacteria and lactobacillus species, and by consuming the high
soluble fiber foods that good bugs like to eat, called “prebiotics.”
4- Repair:
Help the lining of the GI tract repair itself by supplying key nutrients that
can often be in short supply in a disease state, such as zinc, antioxidants
(e.g. vitamins A, C, and E), fish oil, and the amino acid glutamine.
5- Rebalance:
Pay attention to lifestyle choices – sleep, exercise and stress can all
affect the GI tract.
5-R Program
Elements for digestive health are described briefly below

66. Microbiota Accessible Carbohydrates
Soluble fibers
• Fruits and vegetables e.g. apples, pears, berries, carrots, squash,
zucchini, sweet potato
Non-starch polysaccharides
• Long chain carbohydrates that are not starch e.g. onions, garlic,
Jerusalem artichoke, leeks
Resistant starch
• Non-soluble fiber e.g. beans, legumes, lentils, cooked-cooled
potatoes, plantains
Microbiota-accessible carbohydrates (MACs) are carbohydrates that are resistant to digestion by a host's
metabolism, and are made available for gut microbes, as prebiotics, to ferment or metabolize into beneficial
compounds, such as short chain fatty acids.

67. To get the fiber your body needs, eat
a well-balanced diet that includes
delicious high-fiber foods likes
these:
FRUITS.
bananas, oranges, apples, mangoes,
strawberries, raspberries.
VEGETABLES.
Generally, the darker the color, the
higher the fiber content. ...
BEANS & LEGUMES. ...
BREADS & Whole GRAINS. ...
NUTS.

68. Courtesy Kathie Swift MS RDN LDN FAND EBQ

69. Courtesy Kathie Swift MS RDN LDN FAND EBQ

71. Courtesy Kathie Swift MS RDN LDN FAND EBQ

72. Peppermint
Kill Mouth Germs
Fight Food borne Bacteria
like E. coli, listeria, and salmonella. They found that it can stop all
three from growing. It can also kill Staphylococcus aureus, a
bacteria that causes skin infections, pneumonia, meningitis, and
more.sd
Apple Cider Vinegar
Acidifying the stomach
Kill pathogens, including bacteria
Garlic
Anti-bacterial
Anti-parasitic
Curcumin is the key active ingredient in turmeric
Antioxidant
Anti-inflammatory
Antimicrobial
Antifungal activities

73. Lifestyle changes to bring diversity and
balance to the gut microbiome 1
• Diminish sugar and processed refined, carbohydrate-dense foods. Grains, gluten
and Glyphosate exposures
• Increase fermentable plant-based fiber and fermentable foods
• Biodiversity in food and feed.
• Fermented foods containing lactobacilli : include many ancient staples,
ranging from fermented milk, yogurt, cheese and wine to olives,
pickles, sauerkraut, sourdough bread, fermented sausages and salami, as
well as silage and recent probiotic dairy products. Apr 7, 2006
• foods containing bifidobacteria : Eat whole grains: Whole grains such as
oats and barley are very good for gut health and can help increase intestinal
Bifidobacteria (43, 44). Eat fermented foods: Fermented foods such
as yogurt and kimchi contain healthy bacteria. Jul 25, 2017

74. • Whenever possible, go organic, GMO-free (Glyphosate)
• Cautious with prescribed antibiotics and feed lot meats, poultry, and eggs
• Minimize NNS non-nutritive sweeteners, emulsifiers, thickeners
• Consider: testing, diagnosis and treatment of dysbiosis-SIBO (SIBO breath
testing; Complete Digestive Stool Analysis (CDSA) ; H. pylori)
• Probiotics
• Taper, d/c PPIs
• ? Future of fecal microbiota transplants
Lifestyle changes to bring diversity and
balance to the gut microbiome 2

76. Main References:
How epigenetics, our gut microbiome and the environment interact to change our lives
Ben Locwin | Genetic Literacy Project | October 17, 2016
Health and the Gut Microbiome: Restoring a Lost Legacy
Mark Pettus MD. Director of Medical Education and Population Health. Berkshire Health
Systems. March 27, 2017
The Fungal Mycobiota: Small Numbers, Large Impacts
Carol A. Kumamoto1,*
1Department of Molecular Biology and Microbiology, Tufts University, 150 Harrison Avenue,
Boston, MA 02111, USA
*Correspondence: carol.kumamoto@tufts.edu
http://dx.doi.org/10.1016/j.chom.2016.05.018
Fungal dysbiosis: immunity and interactions at mucosal barriers
Iliyan D. Iliev
1,2,3
and Irina Leonardi
1,3
Nat Rev Immunol. 2017 Oct; 17(10): 635–646.
Published online 2017 Jun 12. doi: 10.1038/nri.2017.55
The Fungal Mycobiome and Its Interaction with Gut Bacteria in the Host
Qi Hui Sam 1
,Matthew Wook Chang 2,3
Int. J. Mol. Sci. 2017, 18(2), 330; doi:10.3390/ijms18020330
Systemic candidiasis Other Names: Systemic candida infections; Invasive Candidiasis
Genetic and Rare Diseases Information Center (GARD)

77. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases
Lan Lin1*Lin and Zhang BMC Immunology (2017) 18:2
DOI 10.1186/s12865-016-0187-3
Immunological Consequences of Intestinal Fungal Dysbiosis
Matthew L. Wheeler,1 Jose J. Limon,1 Agnieszka S. Bar,1,6 Christian A. Leal,1 Matthew
Gargus,1 Jie Tang,2 Jordan Brown,2
Vincent A. Funari,2 Hanlin L. Wang,3 Timothy R. Crother,4 Moshe Arditi,4 David M.
Underhill,1,3,5,* and Iliyan D. Iliev1,5,6,*
The Mycobiome: A Neglected Component in the Microbiota-Gut-Brain Axis
Raphaël Enaud 1,2,3,*, Louise-Eva Vandenborght 1,3,4, Noémie Coron 1,2,3, Thomas Bazin
1,2, enaud Prevel 1, Thierry Schaeverbeke 1,2, Patrick Berger 1,2,3, Michael Fayon 1,2,3,
Thierry Lamireau 1,2 ID and Laurence Delhaes 1,2,3
Received: 5 February 2018; Accepted: 5 March 2018; Published: 9 March 2018
Role of the gut microbiota in nutrition and health
Article (PDF Available) in BMJ Clinical Research 361:k2179 · June 2018 with 286 Reads
DOI: 10.1136/bmj.k2179
JB Review J Biochem 127, 717-722 2000: The Function of Vitamin D Receptor in
Vitamin D Action
Shigeaki Kato Institute of Molecular and Cellular Biosciencex The University of Tokyo, Yavoi-
cho, Bunkyo-ku, Tokyo, 113-0032; and CREST, Japan Science and Technology Corporation,
41-8 Honcho, Kawaguchi, Saitama 332 Received January 21, 2000; accepted January 28,
2000