Science behind Pathogenesis


Microbes in the human body



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Successive infection and variability in disease

Related article: Familial aggregation


Over the course of a lifetime, patients pick up the approximately 90 trillion bacteria to which they play host.4) While some researchers refer to each person's unique microbiota as an individual's “pathogen burden” and other terms,5) 6) we have referred to it as a person's “pea soupThe unique combination of bacterial pathogens (and co-mingling of bacterial genes) which accounts for each individual’s disease presentation..” In everyday language, the term pea soup is otherwise used to refer to a dense fog – an apt metaphor for the human microbiota. The promiscuity with which bacteria exchange DNA as well as the sheer number of bacteria to which any given person plays host are both factors which severely limit researchers' ability to accurately predict species-species and species-disease interactions.


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Transmission of chronic disease

Related article: Familial aggregation




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Koch's postulates

Main article: Koch's posutlates

Related article: Detecting bacteria

Microbiologist Robert KochAuthor of Koch's postulates, a set of rules for establishing a relationship between a causative microbe and a disease. Koch's belief that only one pathogens causes one disease has now been called into question as multiple postulates are increasingly considered out of date. was born in 1843. Koch's postulatesCentury-old criteria designed to establish a causal relationship between a causative microbe and a disease. Koch's belief that only one pathogen causes one disease has now been called into question as multiple postulates are increasingly considered out of date. are a series of ground rules to determine whether a given organism can cause a given disease. Koch theorized that a pathogen must be:

  • found in all cases of the disease examined
  • prepared and maintained in a pure culture
  • retrievable from an inoculated animal and cultured again

For all their lingering influence, Koch's postulates never anticipated the era of the human metagenome in which thousands of difficult or impossible-to-culture species of bacteria contribute to a single disease state. Koch's century-old ideas have held science back from understanding how chronic disease occurs because they make no provision for these facts.

The Marshall Pathogenesis is consistent with mounting evidence that Koch's postulates no longer apply to discerning the vast amounts of microbes in the human body.

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Horizontal gene transfer

Main article: Horizontal gene transfer

Horizontal gene transferAny process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. (HGT), sometimes referred to as lateral gene transferAny process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. Also referred to as horizontal gene transfer., is any process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. HGT represents a substantial blow to the validity of Koch's postulatesCentury-old criteria designed to establish a causal relationship between a causative microbe and a disease. Koch's belief that only one pathogen causes one disease has now been called into question as multiple postulates are increasingly considered out of date., which state that any given infectious disease is caused by a single discrete and well-defined pathogen.

Increasingly, studies of genes and genomes are indicating that considerable horizontal gene transfer has occurred between bacteria.

James Lake, Molecular Biology Institute at the University of California

In fact, due to increasing evidence suggesting the importance of the phenomenon in organisms that cause disease, molecular biologists such as Peter Gogarten at the University of Connecticut have described horizontal gene transfer as “a new paradigm for biology.“

Gorgarten insists that horizontal gene transfer is “more frequent than most biologists could even imagine a decade ago” and that this reality turns the idea that we can classify organisms in a simple “tree of life” on its head.

Instead Gogarten suggests that biologists use the metaphor of a mosaic to describe the different histories combined in individual genomes and use the metaphor of a net to visualize the rich exchange of DNA among microbes.

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Innate immune response and Th1 inflammation

The innate immune response is the body's first line of defense against and a non-specific way for responding to bacterial pathogens.7) Located in the nucleus of a variety of cells, the Vitamin D nuclear receptor (VDR) plays a crucial, often under-appreciated, role in the innate immune response. The vitamin D receptor and T cell function

When functioning properly, the VDR transcribes between hundreds8) and thousands of genes9) including those for the proteins known as the antimicrobial peptides. Antimicrobial peptides are “the body's natural antibiotics,” crucial for both prevention and clearance of infection.10) The VDR also expresses the TLR2 receptor, which is expressed on the surface of certain cells and recognizes foreign substances.

The body controls activity of the VDR through regulation of the vitamin D metabolites. 25-hydroxyvitamin D (25-D) antagonizes or inactivates the Receptor while 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. (1,25-D) agonizes or activates the Receptor.

Greater than 36 types of tissue have been identified as having a Vitamin D Receptor.11)

Another component of the innate immune response is the release of inflammatory cytokines. The result is what medicine calls inflammation, which generally leads to an increase in symptoms.

Before the Human MicrobiomeThe bacterial community in the human body. Many species in the microbiota contribute to the development of chronic disease. Project, scientists couldn't link bacteria to inflammatory diseases. But with the advent of DNA sequencing technology, scientists have detected many of the bacteria capable of generating an inflammatory response. All diseases of unknown etiology are inflammatory diseases.

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Vitamin D

Main article: Science behind vitamin D

A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin D (25-D) and that consuming greater quantities of vitamin D, which further elevates 25-D levels, alleviates disease symptoms.




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Th1 Spectrum Disorder

Main article: Th1 Spectrum Disorder





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Incidence and prevalence of chronic disease

The last half century has seen a steady increase in the incidence and prevalence of chronic inflammatory diseases with further increases expected. According to the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., a number of factors are to blame:

  • misuse of antibiotics especially Beta-lactam antibiotics
  • vitamin supplementation including folic acid but especially vitamin D
  • presence of environmental factors which suppress immunity
  • novel vectors for sharing pathogens including blood donation
  • widespread adoption of compulsory mass vaccinations

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Familial aggregation

Main article: Familial aggregation

Familial aggregationOccurrence of a given trait shared by members of a family (or community) that cannot be readily accounted for by chance. refers to occurrence of a given trait shared by members of a family that cannot be readily accounted for by chance. For example we hear that certain diseases “run” in families, or we note that an entire family unit suffers from an inflammatory disease such as obesity. While it has long been understood that acute infections like tuberculosis, polio, and HIV are communicable, it is less well appreciated that the same can be said for the chronic pathogens which cause Th1 diseases.


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Evolutionary perspective on disease


Generally speaking, diseases have three major causes: genetic, environmental, and infectious. Each disease affects, to some degree, an organism's ability to reproduce, that is, their reproductive fitness. As a general rule, infectious disease confers no reproductive benefit but genetic diseases do, either currently or historically.

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Evidence that chronic disease is caused by pathogens



  • researchers' failure to identify any kind of telltale genetic connection in disease in twins and other studies
  • familial aggregation of disease and incidence in small communities in close contact
  • migration studies
  • single region changes in incidence
  • transmission of disease through blood and tissue donation
  • inferential evidence from what is known about evolution and reproductive fitness




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Immune suppression from modern living

Over seven years of research by nine Oldenburg scientists, in cooperation with Prof. Dr. Peter J. Hore of Oxford University

scientists were able to show that the disruptive effects were generated by electromagnetic fields that cover a much broader frequency range at a much lower intensity than previous studies had suggested. This electromagnetic broadband interference is omnipresent in urban environments. It is created wherever people use electronic devices

In a 2014 article in Nature, Prof. Dr. Henrik Mouritsen, a biologist and Lichtenberg Professor at the University of Oldenburg stressed



the effect of anthropogenic electromagnetic noise on bird migration is localised. However these findings should make us think – both about the survival of migratory birds as well as about the potential effects for human beings, which have yet to be investigated,

France is leading the world in the precautionary principle

Alternate models for chronic disease

The evidence supporting a bacterial cause for chronic disease is strong. Still, there are other competing explanations including the acid/alkaline imbalance theory, autoimmune disease theory, the genetic predisposition theory, the single pathogen theory, and the spontaneous remission theory. Some have argued that viral co-infections are to blame for diseases of unknown etiology despite the evidence which has accumulated to the contrary.

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Notes and comments

  • Legacy content


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Antimicrobial peptides of multicellular organisms.
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