elite controllers

Elite Controllers hypothesis. Human as a holobiont and AIDS paradigm.

Elite Controllers hypothesis. Human as a holobiont and AIDS paradigm.

by Marcin Regulski, 2018 Jul 26

In memory of Freddie Mercury

Summary.
Understanding the secret of Elite Controllers.

Among the HIV infected individuals some aren’t progressive to AIDS, their immune system keeps viral
load as low as patients on successful ARV therapy. In fact some of them are doing so well that
according to professor Steven G. Deeks from San Francisco General Hospital “no one has proven
Elite Controllers have not cleared their virus, in which case this becomes an extremely important
group to study”. Some of his patients using conventional blood tests, show no HIV virus. “but you
can’t prove a negative”.[1]

Latest research on human genome shows we should revise knowledge on how our immune system
works. This new point of view is looking at human as a holobiont entity, because humans consist of
thousands of microbial species. Some of them have critical influence on our immune system.
Animals and plants are no longer described as single entities but rather as biomolecular networks
composed of the host plus its associated microbes. [2]

Looking through latest research we can point to some of them as possible answer to Elite Controllers
secret. If this is going to be good pick, probably all infected individuals could become an Elite
Controllers, most probably finally clearing their dormant virus.

But this theory emerges another question, how to preserve this unique ability of Elite Controllers for
a lifetime? The answer may be quite shocking but it opens new field of understanding possibility to
treat other conditions as cancers, auto immunologic diseases and possibly many more.

Introduction
Host Biology in Light of the Microbiome

microbiome

Groundbreaking research on the universality and diversity of microorganisms is now challenging the
life sciences to upgrade fundamental theories that once seemed untouchable. To fully appreciate the
change that the field is now undergoing, one has to place the epochs and foundational principles of
Darwin, Mendel, and the modern synthesis in light of the current advances that are enabling a new
vision for the central importance of microbiology. Animals and plants are no longer heralded as
autonomous entities but rather as biomolecular networks composed of the host plus its associated
microbes, i.e., “holobionts.” As such, their collective genomes forge a “hologenome,” and models of
animal and plant biology that do not account for these intergenomic associations are incomplete.

At a time when symbiotic microbes are recognized as fundamental to all aspects of animal and plant
biology, the holobiont and hologenome concepts afford a holistic view of biological complexity that is
consistent with the generally reductionist approaches of biology. Rather than transforming
evolutionary thought, the hologenome concept develops it in a substantive and timely way. From a
specific standpoint, the holobiont and hologenome concepts redefine that which constitutes an
individual animal or plant by asserting that hosts and their symbiotic microbes are complex units of
biological organization upon which ecology and evolution can act. From a general standpoint, the
concepts assert that microbe evolution has been driven by both population and community genetics
and that symbiotic microbes and nuclear genes hold equivalent significance in the origin of new
holobiont species. [2]

Bacteria in your body

Up to 2.5% of your body’s weight consists of bacteria. Bacteria have lived in and on all
animals since life evolved. About 1000 different strains of bacteria, yeasts, protozoa and other
microorganisms weighing over 2 kg live in your body [3]. Most of them are in your digestive tract,
but they are also in your nose, throat, ears, eyes, skin, genitals, urethra and throughout your body.
It is essential to have good bacteria on your throat, urethra, nasal passages, vaginal walls etc. [4]
They play an critical part in your immune system, and protect you from invading pathogenic
bacteria, fungi and viruses. Bacteria are resident on all your membranes, protecting you against
infection. Bacteria play an essential role in your digestion – without them, you cannot break down
many foods and absorb the nutrients. Having the right bacteria in your gut helps organs all over
your body function correctly, including your brain. Studies [5, 6, 7] confirm the protective effects
of probiotic bacteria against depression and other brain maladies. Bacteria assist in the production
of some vitamins (B12, K, etc). The bacteria, fungi, protozoa and other microflora making up your
microbiome are essential for life and good health, and a healthy balance (symbiosis) is built up
over your lifetime [3]. This symbiosis is helping us digesting foods, metabolizing vitamins, sugars,
fats and amino acids, enhancing our immune system, and protecting us from other pathogenic
bacteria or fungi. Together with viruses and fungi that reside inside us they form our microbiome.
Disruption of the delicate balance of our microbiota can lead to a whole range of health problems,
such as inflammatory bowel disease, obesity, colitis, cancer, bacterial vaginosis, strep throat, ear
infection, nose congestion, eczema, chronic fatigue syndrome, and more. This phenomenon is
known as dysbiosis. Any bacteria is potentially pathogenic if it enters the bloodstream or set up
residence within our organs. When this happens, however, our immune system reacts
immediately and gets rid of the invaders. The interaction between the immune system and our
microbiota is what keeps us healthy and makes us sick. That is possible the single most important
thing to know about one’s health, and yet until recently it was impossible to know what bacteria
lived on our bodies. Leakage of microbes from the gut as a result of HIV-related damage to the
wall of the gut may be one of the major causes of the systemic immune activation that drives the
HIV disease process, according to a United States-led research group reporting in Nature Medicine.

HIV microbiome

 

Understanding gut microbiota alterations associated with HIV infection and factors that drive
these alterations may help explain gut-linked diseases prevalent with HIV. HIV-1 infection induces
rapid and substantial damage to gut-associated lymphoid tissues (GALTs), with massive depletion
of Th17 cells, a subset of CD4+ T cells that control intestinal bacteria (Brenchley et al., 2004). Loss
of this CD4+ T cell subset may facilitate disease progression by allowing translocation of bacterial
products such as lipopolysaccharide to blood, causing systemic T cell activation (Brenchley et al.,
2006). In healthy individuals, intestinal bacteria help control harmful pathogens, educate the
immune system, and aid in digestion (Lozupone et al., 2012), but distinctive compositions of this
complex community have been associated with pathologies that are of increased prevalence with
HIV infection, including metabolic disorders (Madge et al., 1999, Vijay-Kumar et al., 2010), chronic
inflammation (Bjarnason et al., 1996, Willing et al., 2010), wasting/malnutrition (Smith et al.,
2013, Wanke et al., 2000), atherosclerosis (Hsue et al., 2009, Koeth et al., 2013), and susceptibility
to opportunistic infections (Chang et al., 2008). The fecal microbiota of untreated individuals with
chronic infection exhibited significantly higher relative abundances of compared to HIV negative
HIV-negative individuals had increased Bacteroidaceae (Bacteroides) . [8]

 Can depletion of Bacteroidaceae in uninfected person have the same impact on overall health as in HIV infected ones?

Maybe that is why You don’t have to be HIV positive to get kaposi sarcoma or TB? This suggests that there may be other
than HIV cause of such microbiota changes. When we realise that healty micriobiota that
resembles microbiota of uninfected human, keep immune system so effective that it can
potentially control viral load as Elite Controllers then we should reconsider what really causes
AIDS. Is it HIV infection or not reversed microbiota changes after infection?

We should take a closer look at some of known Bacteroides species to see if loss of them may
possible impact host immune system function. Comparing possible similiarities to microbiota
alterations in Elite Controllers may give interesting conclusions.
Alternative mechanism for antigen presentation
Bacteroides fragilis, is in a genus that consistently and dramatically decreases with HIV infection.
This species, and specifically a zwitterionic polysaccharide (ZPS) on its capsule called
polysaccharide A (PSA), restores CD4+ T cell development in germ-free mice by eliciting expansion
of antigen-experienced (“educated”) CD4+CD45Rblow T cells (Mazmanian et al., 2005). Depletion of
CD4+ T cells is main indicator of loosing immune system capabilities in HIV infected individuals
while Elite Controllers keep Bacteroides level high enough to keep activating CD4+ thus holding
immunity at level as uninfected subjects. B. fragilis PSA can also mediate conversion of CD4+
T cells into anti-inflammatory Foxp3+ Treg cells (Round and Mazmanian, 2010) and can provide
protection from inflammatory disease (Mazmanian et al., 2005, Mazmanian et al., 2008).When
administered as a probiotic, another Bacteroides species, B. uniformis, can correct T cell
proliferation deficiencies displayed in “Western diet”-fed mice (Gauffin Cano et al., 2012) and
induces higher secretion of IL-10, a negative regulator of inflammatory response.

It has also been shown that exposure to ZPSs induces the expression of MHC class II molecules. On
the basis of computer-modelling studies, Dennis L.Kasper and collegues proposed that PSA might
form a complex with MHC by docking onto α-helices that make up the lateral boundaries of the
peptide-binding groove of MHC molecules. And, on the basis of these data the idea was put
forward that perhaps PSA a pure polysaccharide is displayed on MHC molecules and presented to
the T-cell receptor (TCR) of CD4+ T cells, a mechanism that was previously thought to apply
exclusively to protein antigens. Could this mean that PSA displayed on MHC molecules are
recognized by T cells? It had been shown that there are forms of antigen presentation other than
display of peptides by MHC molecules.

Results indicate an alternative to the paradigm protein-antigen processing presentation, and they
illustrate how polysaccharides can be presented by MHC class II molecules to activate CD4+ T cell
responses. Therefore, the mechanism by which ZPSs mediate their effort on T cells is as unique as
their structure. Results show that PSA of B.fragilis a ubiquitous symbiotic bacterium in all
mammals, is necessary and sufficient to mediate the generation of a normal mature immune
system. [9] This way of presenting antigens to lymphocytes is a possible solution for immune
system to produce broadly neutralizing antibodies without infecting T cells, just like Elite
Controllers do. B.fragilis clearly influences the immune response that is aimed at neutralizing most,
if not all, other colonic microorganisms and therefore at preventing serious or even life-
threatening bacteraemia after intestinal trauma. It has recently been shown that other
Bacteroides species induce the expression of antimicrobial molecules that directly bind and
eliminate potentially pathogenic bacteria.
Bacteroides thetaiotaomicron study reveals relationships between intestinal microbiota and the
differentiation and secretory program of colonic goblet cells. We propose that B.
thetaiotaomicron and F. prausnitzii, two main members of microbiota representative of
Bacteroidetes and Firmicutes, contribute to the establishment of epithelial homeostasis. These two
bacteria, which are metabolically complementary, modulate in vivo the intestinal mucus barrier by
modifying goblet cells and mucin glycosylation. Here we show how the balance between B.
thetaiotaomicron and F. prausnitzii could be determinant for maintaining colonic epithelial
homeostasis and health via their respective effects on mucus.[15]. The results indicate that in order
to have a complete and functional immune system, a healthy microbiota must be present.

Gut microbiota diversity is correlated with CD4+ T-cell counts and lowest number of bacterial
species was present among the patients with lowest CD4+ and after introduction of ART we
observe moderate, but significant decrease in number of observed species. The alpha diversity did
not increase after ART with viral suppression. On the contrary, individual microbiota became less
diverse. This points to conclusion that ART is not a way to achieve natural suppression of HIV of
Elite Controllers.[10] Microbiota of Elite Controllers resembles microbiota of healthy individuals.
Modulation of the gut microbiota appears as an exciting perspective to reduce chronic inflammation
and immune activation in infected patients. Administation of Lactobacilli an Bifidobacteria were
reported to decrease systemic immune activation markers. Increase of T-Lymphocytes had also been
yielded after supplementation with Lactobacilli. Increase of T-lymphocytes had been also yielded
after supplementation with Lactobacilli. Besides, administration of Saccharomyces boulardii
decreased inflammation parameters and microbial translocation in patients virologically suppressed
[12]. Finally, a systematic review dedicated to the evaluation of daily probiotic use revealed that 7
out of 13 included studies reported improvement of CD4 T cell count. ascorbic acid along with
Nacetylcysteine reduces early apoptosis of CD4 + T-cell induced by LPS as selenium increases
glutathione peroxidase activity in latently infected T-cells, which become protected from hydrogen
peroxide cytotoxic effect [13]. Human studies are also concerned, as vitamin supplementation
including vitamin A in early stage of the disease lessens HIV progression and delays the introduction
of ART. The literature currently offers several exciting perspectives, and the modulation of the
microbiome will probably be a significant part of HIV therapeutics in the future. [11]

Cancer

Cross disciplinary studies shows an interesting conclusion that is relevant to EC hypothesis:

“UT Southwestern cancer researchers analyzed gut bacteria of 39 melanoma patients who were
treated with immunotherapies and found strong association between a good response and the
presence of particular bacteria.

As a group, patients who responded well to the immunotherapy had three specific bacteria:
Bacteroides thetaiotaomicron
Faecalibacterium prausnitzii
Holdemania filiformis
All three are common normal flora in the human intestinal tract. “While these preliminary
observations do not establish a firm causal connection between gut microbes and immunotherapy
efficacy, they may lead eventually to a probiotic cocktail that could be given along with
immunotherapy to enhance the chance of response,” said Dr. Koh, Director of Pediatric
Hematopoietic Stem Cell Transplantation at UT Southwestern.”[14]

This new perspective leds to conclusion that bacteroides are critical to properly functioning immune
system. It’s quite simple to introduce these species into gastrointestinal tract. Simpliest way to
prove this hypotesis is to perform fecal mikrobiota transplant, with Elite Controller as a donor.
Figure 2.

If bacteroides are right pick for Elite Controllers ability to control viral load, it is certain that it will
eventually stop progress to AIDS. Bacteroides fragilis is critical element of mechanism that produces
broadly neutralizing antibody. The same occurs in other viral infections, HCV is similar. Some HCV
patients who are self-cured, the Th1 type is predominant.[Fig 2] It is strong, highly specific and broad,
i.e. directed against many epitopes of structural and non-structural HCV proteins with a high degree
of conservativeness. Because Immune system doesn’t diferentiate viruses to get rid of. Without
bacteroides fragilis overall viruses, parasites count load is high and this overall overload is real cause
of progress to AIDS.
That is all.

My effort to find a solution and cure for AIDS is an ultimate quest for me.
And I’m granting results of my research to You.
There is second part of this document, it contains knowledge on how to heal Yourself and to rise CD4
count. It’s also what You mustn’t do.

If You would like to show me gratitude for what You’ve read I would be very pleased to receive any
donation to support my further work. I wish I could start new project to exchange knowledge on our
health in light of microbiome.
My target is I could send You bacterial mix to restart You immune system as an Elite Controller.

I wish to thank every author of work I quoted to compile this document.

Deus vult.
UGLY PART 2

The result of taking antibiotics

Regarding fact that microbiom diversity and presence of particular species as B.fragilis and
B.thetaiotaomicron have very strong influence on how HIV infection progress, question arises how
much impact on health of a patient do antibiotics have? When you take an antibiotic, you
indiscriminately destroy most of the friendly microflora in your body in addition to the target
bacteria. There is evidence that the friendly flora that take a lifetime to build up never fully recover.
After taking an antibiotic, you are vulnerable to invasion by bacteria, fungi and viruses. Indeed, some
of the commensal bacteria eliminated by the antibiotic never recovered after antibiotic cessation.
These persistent microbiota changes allowed the pathogen to persist in the intestinal tract.
Importantly, results were obtained in humans. In some of the analyzed subjects, the majority of most
abundant commensal bacteria identified at baseline, could not be detected even 22 weeks after
antibiotic cessation. These results are clinically very relevant, since they indicate that at least some of
the individuals that are treated with certain antibiotics could have permanent changes in their
microbiota, which could subsequently predispose to diseases as AIDS. We were able to demonstrate
that the microbiota can confer resistance to Antibiotics Resistant Pathogens in the absence of a
proper innate immune response (Toll like and NOD receptors) or adaptive response (B and T cells).
These last results suggest that other mechanisms not dependent on the immune response may be
crucial for the defense against Antibiotics Resistant Pathogens. These mechanisms may include the
production of molecules by commensal microbes that could inhibit the growth of the pathogen or
interfere with its behavior, or nutrient competition between commensals and pathogens. [1]

A ground-breaking study (14) published in 2017 showed that a standard course of antibiotics given to
pregnant mice and young pups permanently altered their brains and their behaviour. The young
mice were aggressive and less sociable.

The study also noted the strong association between antibiotics and irritable bowel syndrome
(IBS), obesity, and a wide range of psychiatric disorders.

The good news shown by this study was that most of this damage did not occur in a group of
mice that were fed probiotics during the antibiotic course!

Bacteroides fragilis is another example of a beneficial bacteria that is being wiped out. B.
fragilis moderates the immune system and prevents excessive inflammation. The absence of this
bacteria is likely responsible for a significant increase in many autoimmune disorders such as Crohn’s
disease, type I diabetes and multiple sclerosis.

“The antibacterial activity of metronidazole was discovered by accident in 1962 when metronidazole
cured a patient of both trichomonad vaginitis and bacterial gingivitis. However, it was not until the
1970s that metronidazole was popularized for treatment of infections caused by gram-negative
anaerobes such as bacteroides or gram-positive anaerobes such as clostridia.”[25]

Maybe it’s a coincidence but Metronidazole was introduced on market on the 1970’s just before
AIDS epidemy breakout. If HIV was acquired from monkeys during hunting them for flesh, why did it
happen so late in XX century? People hunt monkeys for more than hundreds of years, and SIV exists
for more than thousands of years. Even if You weren’t prescribed Metronidazole or other
antimicrobial agent by doctor, it is almost sure that You have eaten it with food. Most food
preservatives targets anaerobic bacteria species. You should avoid it.

“Here are some of the problems that can arise from bacterial imbalance. The level of these diseases
have more than doubled in many populations in line with the increased use of antibiotics [16]. This
list is not complete – I suspect that many more degenerative diseases have a lack of beneficial
bacteria, or a bacteria imbalance as their root cause.

Questions:

Does other antibiotics that wipes out anaerobic commensal bacteria that are critical to immune
system eventually causes cancer?

What happens to immune system of a person freshly infected with HIV which acute infection is
misdiagnosed as flu and doctor prescribes antibiotic that eventually kills bacteroides?

Are antibiotics real cause of AIDS?

Was professor Duesberg right that HIV is not cause of AIDS?
Here is what You can do:

Get Your microbiome scanned. There are few labs that do such diagnose.

Find a doctor that will help You restore healthy microbiota. Fecal transplant with EC as a donor could
be the right step.