Advertisements
Feeds:
Posts
Comments

Posts Tagged ‘lactose intolerance’


Natural Drug Target Discovery and Translational Medicine in Human Microbiome

Author and Curator: Demet Sag, PhD

 

Remember Ecology 101, simple description of ecosystem includes both living, biotic, and non-living, abiotic, that response to differentiation based on external and internal factors.  Hence, biodiversity changes since living systems are open systems and always try to reach stability. Both soil and human body are rich in microbial life against ever changing conditions. Previously, discovery of marine microorganisms for treatment of complex diseases especially cancer and drug discovery for pharmaceutical applications was discussed. (https://pharmaceuticalintelligence.com/2014/03/20/without-the-past-no-future-but-learn-and-move-genomics-of-microorganisms-to-translational-medicine/)

Here, the focus will be given to clinical drug discovery based on how lactose intolerance and human microbiome related to treat cancer patients or other diseases. In sum, creating clinical relevance with human microbiome require knowledge of both of the worlds to make best of it to solve complex diseases naturally.

The huge undertake as a roadmap to biomedical research originated by NIH under The Human Microbiome Project (HMP) (http://nihroadmap.nih.gov) with 250 healthy individuals as a starting point.  Recent developments opened the doors to pursue us to understand how human microbiome reflects on metabolism, drug interactions and numerous diseases.  Finally, association between clinical states and microbiome are improving with advanced algorithms, bioinformatics and genomics. In classical reading tests questions finding the simile between two groups of words can well relate how microbiome- human and soil-earth relates.  Both are rich in microbial life with quite changing characters to survive through commensal living.

Thus, it is also good to talk about how we can synthesize existing info on interactions between soil microorganisms and decomposers for human diseases and human microbiome. Epidemiology of living organisms is diverse but they all share common interest. In soil, for example, radioactively contaminated soil can’t support plant growth well so Nitrosomonas may support to bring the life to soil through supplying nitrogen. And others can be added to bring a favorable enriched soil.

In human microbiome nutrition-diseases interacts in such a harmony with genetic make up (the information received at time of birth germline- or acquired later in life due to mutations by various reasons). For example, the simplest example is lactose intolerance and the other is development of diabetes.  Generally, it is described as If person is missing a gene to metabolize lactose (sugar) this person become Lactose intolerant yet this can be gained before birth or after. The fix is easy since avoiding certain food groups i.e. milk products.

Yet, this is not that simple!

In human microbiome, the rich gastrointestinal (GI) tract contains many organisms and one of the most important ones is Enterococci that are often simply described as lactic-acid–producing bacteria—by under- appreciation of their power of microbial physiology and outcomes as well as their ubiquitous nature of enterococci.  Schleifer & Kilpper-Bälz, 1984 also reported that the Group D streptococci, such as Streptococcus faecalis and Streptococcus faecium, were included in the new genus called Enterococcus.

The importance of this genius, consists of 37 species, coming from their spectrum of  habitats that include the gastrointestinal microbiota of nearly every animal phylum and flexibility with ability to widely colonize, intrinsic resistance to many inhabitable conditions even though they don’t have spores but they can survive against desiccation and can persist for months on dried surfaces.  Furthermore, they can tolerate extreme conditions such as pH changes, ionizing radiation, osmotic and oxidative stresses, high heavy metal concentrations, and antibiotics.

There is a double sword application as these organisms used as probiotics to improve immune system of the host.  If it is human to prevent contaminated food related diseases or in animals prevent transmitting them to the consumers. Thus, E. faecium and E. faecalis strains are used as probiotics and are ingested in high numbers, generally in the form of pharmaceutical preparations to treat diarrhea, antibiotic-associated diarrhea or irritable bowel syndrome, to lower cholesterol levels or to improve host immunity.

When it comes to human body within each system specific organs may create distinct values.  For example the pH values of GI tract vary and during diseases since pH levels are not at at correct levels.  As a result, due to mal-absorption of nutrients and elements such as food, vitamins and minerals body can’t heal itself. This changing microbial genomics on the surface of GI reflects on general health.  Entrococcus family among the other GI’s natural flora has the microbial physiology adopt these various pH conditions well. 

 

Our body has its own standards to function, such as  pH, temperature, oxygen etc these are basics so that enzymatic reactions may happen to metabolize,synthesizing (making) or catalyzing (breaking) what we eat.  The pH is the measure of hydrogen-ion concentration  in solution.  For example, human blood has a narrow pH (7.35 – 7.45 ) and below or above this range means symptoms and disease yet if blood pH moves to much below 6.8 or above 7.8, cells stop functioning and the patient dies since the ideal pH for blood is 7.4.  This value is unified.  On the other hand, the pH in the human digestive tract or GI changes tremendously to adopt and carry on its function, the pH of saliva (6.5 – 7.5), upper portion of the stomach (4.0 – 6.5) where “predigestion” occurs, the lower portion of the stomach is secreting hydrochloric acid (HCI) and pepsin until it reaches a pH between 1.5 – 4.0; duodenum, small intestine, (7.0 – 8.5) where 90% of the absorption of nutrients is taken in by the body while the waste products are passed out through the colon (pH 4.0 – 7.0).

 

Why is pH important and how related to anything?

Development and presence of cancer always require an acid pH and lack of oxygen.  Thus, prevention of these two factors may be the key for treatment of cancer as it progress the acidity increases such that the level raises even up to 1000 more than normal levels.

Mainly, due to Warburg effect body opt to get its energy from fermentation of glucose and produce lactic acid that decreases the body pH from 7.3 down to 7 then to 6.5 in advanced stages of cancer.  Furthermore, during metastases this level even reaches to 6.0 and even 5.7 where body can’t fight back with the disease. (Warburg effect is well explained previously by Dr. Larry Berstein (www.linkedin.com/pub/larry-bernstein/38/94b/3aa).

How to bypass the lack of oxygen naturally?

One of the many solution can be a natural solution. The nature made the hemoglobin carrying bacteria, Vitreoscilla hemoglobin (VHb), which is first described by Dale Webster in 1966. The gram negative and obligate aerobic bacterium, Vitreoscilla synthesizes elevated quantities of a homodimeric hemoglobin (VHb) under hypoxic growth conditions.   The main role is likely the binding of oxygen at low concentrations and its direct delivery to the terminal respiratory oxidase(s) such as cytochrome o.  Then, after 1986 with detailed description of the molecule other hemoglobins and flavohemoglobins were identified in a variety of microbes, indicating the widespread occurrence of Hb-like proteins.   Currently, it is the most studied bacterial hemoglobin with application potentials in biotechnology.

It is a plausible solution to integrate Vitroscilla and Enterobacter powers for cancer detection and treatment naturally with body’s own microbiome.

However, there are many microbial organisms and differ person to person based on gender, age, background, genetic make-up, food intake, habits, location etc.  The huge undertake as a roadmap to biomedical research originated by NIH under The Human Microbiome Project (HMP) (http://nihroadmap.nih.gov) with 250 healthy individuals as a starting point.

There were three goals in the agenda of The Human Microbiome Project (HMP) simply:

 1. Utilize advanced high throughput technology,

2. Identify any association between microbiome and disease/health stages,

3. Initiate scientific studies to collect more data.

In sum, creating clinical relevance with human microbiome require knowledge of both of the worlds to make best of it to solve complex diseases naturally.

Previously  Discussed:

AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo
Reporter-Curator: Stephen J. Williams, Ph.D.
https://pharmaceuticalintelligence.com/2013/03/12/ampk-is-a-negative-regulator-of-the-warburg-effect-and-suppresses-tumor-growth-in-vivo/

Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?
Author: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-cause-or-the-effect-of-cancer-a-21st-century-view/

Otto Warburg, A Giant of Modern Cellular Biology
Reporter: Larry H Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/11/02/otto-warburg-a-giant-of-modern-cellular-biology/

Targeting Mitochondrial-bound Hexokinase for Cancer Therapy
Author: Ziv Raviv, PhD
https://pharmaceuticalintelligence.com/2013/04/06/targeting-mito…cancer-therapy

Nitric Oxide has a ubiquitous role in the regulation of glycolysis -with a concomitant influence on mitochondrial function
Curator, Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/09/16/nitric-oxide-has-a-ubiquitous-role-in-the-regulation-of-glycolysis-with-a-concomitant-influence-on-mitochondrial-function/

Potential Drug Target: Glucolysis Regulation – Oxidative stress-responsive microRNA-320
Reporter: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2012/07/25/potential-drug-target-glucolysis-regulation-oxidative-stress-responsive-microrna-320/

Differentiation Therapy – Epigenetics Tackles Solid Tumors
Author-Writer: Stephen J. Williams, Ph.D.
https://pharmaceuticalintelligence.com/2013/01/03/differentiation-therapy-epigenetics-tackles-solid-tumors/

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition
Reporter-Curator: Stephen J. Williams, Ph.D.
https://pharmaceuticalintelligence.com/2012/11/30/histone-deacetylase-inhibitors-induce-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells/

Mitochondrial Damage and Repair under Oxidative Stress
Curator: Larry H Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/10/28/mitochondrial-damage-and-repair-under-oxidative-stress/

Mitochondria: Origin from oxygen free environment, role in aerobic glycolysis, metabolic adaptation
Curator: Larry H Bernsatein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/09/26/mitochondria-origin-from-oxygen-free-environment-role-in-aerobic-glycolysis-metabolic-adaptation/

Expanding the Genetic Alphabet and Linking the Genome to the Metabolome
Reporter& Curator: Larry Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/09/24/expanding-the-genetic-alphabet-and-linking-the-genome-to-the-metabolome/

What can we expect of tumor therapeutic response?
Author: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2012/12/05/what-can-we-expect-of-tumor-therapeutic-response/

A Second Look at the Transthyretin Nutrition Inflammatory Conundrum
Larry H. Bernstein, MD, FACP
https://pharmaceuticalintelligence.com/2012/12/03/a-second-look-at-the-transthyretin-nutrition-inflammatory-conundrum/

 

Further  Readings and References:

Palmer KL, van Schaik W, Willems RJL, Gilmore MS. “Enterococcal Genomics Enterococci: From Commensals to Leading Causes of Drug Resistant Infection.” 2014-.2014 Feb 8

Franz CM, Holzapfel WH, Stiles ME. Enterococci at the crossroads of food safety?

Int J Food Microbiol.” 1999 Mar 1; 47(1-2):1-24.

Franz CM, Huch M, Abriouel H, Holzapfel W, Gálvez A.Int J Food Microbiol. “Enterococci as probiotics and their implications in food safety.” 2011 Dec 2; 151(2):125-40. Epub 2011 Sep 8.

Kayser FH.”Safety aspects of enterococci from the medical point of view.” Int J Food Microbiol. 2003 Dec 1; 88(2-3):255-62.

Webster DA, Hackett DP (1966). “The purification and properties of cytochrome o fromVitreoscilla“. J Biol Chem 241 (14): 3308–3315

Stark BC, Dikshit KL, Pagilla KR (2011). “Recent advances in understanding the structure, function, and biotechnological usefulness of the hemoglobin from the bacterium Vitreoscilla“. Biotechnol Lett 33 (9): 1705–1714

Stark BC, Dikshit KL, Pagilla KR (2012). “The Biochemistry  of Vitreoscillahemoglobin“. Computational and Structural Biotechnology Journal 3 (4): e201210002.

Brenner K, You L, Arnold F. (2008). “Engineering microbial consortia: A new frontier in synthetic biology.” Trends in Biotechnology 26: 483489.

Dunbar J, White S, Forney L. (1997). “Genetic diversity through the looking glass: Effect of enrichment bias.Applied and Environmental Microbiology 63: 13261331.

Foster J. (2001). “Evolutionary computation Nature Reviews Genetics 2: 428436.

Dinsdale EA, et al. 2008. “Functional metagenomic profiling of nine biomes.” Nature452: 629632.

Gudelj I, Beardmore RE, Arkin SS, MacLean RC. (2007). “Constraints on microbial metabolism drive evolutionary diversification in homogeneous environments.” Journal of Evolutionary Biology 20: 1882–1889.

Haack SK, Garchow H, Klug MJ, Forney L. (1995). “Analysis of factors affecting the accuracy, reproducibility, and interpretation of microbial community carbon source utilization patterns.” Applied and Environmental Microbiology 61: 14581468.

Lozupone C, Knight R. (2007). “Global patterns in bacterial diversity.” Proceedings of the National Academy of Sciences 104: 1143611440.

Thurnheer T, Gmr R, Guggenheim B,  (2004). “Multiplex FISH analysis of a six-species bacterial biofilm. “Journal of Microbiological Methods 56: 3747.

VijayKumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S,Sitaraman S, Knight R, Ley RE, Gewirtz AT. (2010). “Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.” Science 328: 228231

Williams HTP, Lenton TM. (2007). “Artificial selection of simulated microbial ecosystems.” Proceedings of the National Academy of Sciences 104: 89188923.

 

 

Advertisements

Read Full Post »