You are the Chosen One, at least by your bacteria

Host genomics is not the main decision-making factor for bacteria immigrating into human body, but  it is an important factor. Two papers recently published in the Proceedings of the National Academy of Sciences help to understand why you are chosen and how the choosers make their decisions.

Benson et al studied microbes of mice C57BL/6J, HR and their offspring. BL6 is a common inbred line prone to diet-induced obesity, type 2 diabetes, and atherosclerosis. They also develop age-related hearing loss, if are not following recommended dietary allowance. High runner (HR) mice is lean and fit and loves to exercise - it's in the genes.

Noninvasive 16S RNA sequencing (Roche 454) showed that the abundance of microbes in "core measurable microbiota" depended on 530 host SNPs, mostly those located in 13 quantitative trait loci and was influenced by 5 more QTLs.

Some of the genetic regions appear to determine what kind of bacteria immigrate and strive in the host, other regions influence the immigration rate, attracting a wide variety pf or specific nationalities. Supplementary material elaborates on  sources of variation and genotype frequencies at given SNP locations. 

How are bacteria making their decisions to colonize or not to colonize?

In another PNAS article, Ben-Jacob and Schultz explain why microbes could be smarter than humans. We may think that our decisions are well thought and sophisticated, but we are, indeed, influenced by other people and our over-interpretations of other people's reactions. Bacteria can assess the noisy and stressful environment around them more objectively and rationally. They anticipate possible drastic changes in the environment and find the best decisions by providing every bacterium with the freedom to choose its own fate. This may look like throwing dice, but the colony manages the odds and effectively programs the effect of the noise on the gene circuit performance.

Our genes may be shaping microbial communities that could, in their turn, control our physical and mental health. Yet our lifestyle choices could break the patterns and let us decide what types of bacteria we want to live with.

And for those whose fight against unwanted microbes is too hard, there may be light in the end of the tunnel: Personal Genomes project has just announced a new collaboration with Rob Knight and Noah Fierer that will enable to explore the microbial diversity of various habitats of the human body and correlate it to the genotype.

References

• Andrew K. Benson,, Scott A. Kelly,, Ryan Legge,, Fangrui Ma,, Soo Jen Low,, Jaehyoung Kim,, Min Zhang,, Phaik Lyn Oh,, Derrick Nehrenberg,, Kunjie Hu,, Stephen D. Kachman,, Etsuko N. Moriyama,, Jens Walter,, Daniel A. Peterson,, & Daniel Pomp10.1073/pnas.1007028107 (2010). Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors Proceedings of the National Academy of Sciences of the United States of America, Published online before print October 11, 2010
• Ben-Jacob E, &; Schultz D (2010). Bacteria determine fate by playing dice with controlled odds. Proceedings of the National Academy of Sciences of the United States of America, 107 (30), 13197-8 PMID: 20660309

Microbial sequencing for food applications is gaining momentum, but challenges remain

Microbes bring us a wide variety of foods, transforming texture and intensifying flavors. Jake Lahne, posted a great overview of some of the good microorganisms in cheese - like Penicillium molds in Cabrales cheese shown on the right - that adds to other ingredients such as milk, salt and coagulants.

While modern cheeses are made with preselected cultures, traditional cheeses carry dozens of types of microbes, some highly unusual and uncharacterized.


Lactic acid bacteria, including lactococci and lactobacilli, not only convert the basic milk sugar, lactose, into lactic acid but also make the cheese inhospitable to many spoilage organisms and is the first step towards deliciousness. Streptococci are also important in cheese and yogurt-making, adding flavor to alpine (Emmental, Gruyere, etc) and Italian hard (Grana Padana, Pecorino Romano, etc) cheeses. Lactococcus lactis, Staphylococcus, Trichococcus, and Monascus are strongly associated with the 36 key aroma compounds of Monascus-fermented cheese. Lactococcus lactis was found to be the dominant bacterium while Monascus was confirmed to be the dominant fungus.

Propionobacter shermanii, are able to digest acetic acid and convert it to sharp, sweaty-smelling propionic acid and carbon dioxide. Several species of propionibacteria also inhabit human skin, producing less wanted odors.

Most of the molds that grow on cheese are species of Penicillium, but some cheeses, like St. Nectaire, develop others such as blue mold, P. roqueforti and P. glaucum in blue cheese. Blues include Roquefort, Stilton, Gorgonzola, and Cabrales, and goat cheese Monte Enebro.
White molds, which are found on the outside of all types of soft-ripened cheeses, are subspecies of P. camembertii (also called P. candidum). These white molds produce enzymes that break down the milk proteins and producing garlicky or earthy, also ammonia smells.

Room-clearing ability of Epoisses, Münster, and Limburger owe to the smear bacteria officially known as Brevibacter linens. They need salty (up to 15%), moist environments to grow,and create stinky odor compounds, producing oniony or garlicky, fishy, and sweaty aromas. The aroma of the washed-rind cheeses is often compared to smelly feet - and, yes, brevibacter grow well on human skin.

But it is not only cheese that carries myriads of microbes. There are many other foods. And not all of the bacteria we consume with the foods is good for you.

Genome sequencing was predicted to bring practical benefits to the field of microbial food safety, identifying and controlling emerging microbial pathogens. It is still not as readily available and inexpensive as needed for practical applications, but a few pilot projects have showed a promise.

GenomeWeb's Andrea Anderson recently published this article about academic researchers and public health agencies exploring the use of genomics-based approaches to complement existing food safety and surveillance methods.

Common foodborne pathogens include E. coli 0157:H7, Salmonella, Listeria, and Campylobacter, but there are many more in need of identification. Having effective ways to distinguish between dangerous and neutral microbes is crucial for food safety.

Many identification methods exist, but whole-genome sequencing could give unprecedented wealth of information, allowing predictions about the nature of organisms, their potential sources and associated risk,

In a paper published in the Journal of Food Protection in May, USDA's Ward and his colleagues reported on their findings from a multi-locus genotyping study of more than 500 Listeria monocytogenes isolates collected by the USDA-FSIS from a variety of ready-to-eat foods.
"Integration of PFGE and DNA-sequence-based sub-typing provides an improved framework for prediction of relative risk associated with L. monocytogenes strains from [ready-to-eat] foods," they wrote.

In another recent paper, Ward and collaborators from Colorado State University used genotyping to show that a virulence-decreasing inlA mutation in L. monocytogenes was more common in isolates from ready-to-eat than from isolates from actual human listeriosis cases.
Honisch presented a poster outlining work done with collaborators from London's Health Protection Agency at the American Society for Microbiology annual meeting in San Diego this May, describing how the team used the Sequenom MassArray platform to do multi-locus sequence typing, or MLST, on hundreds of Salmonella isolates. Honisch told GWDN that the approach is promising, in part, because mass spec is high-throughput and generates very reproducible data.
During a session at the recent ASM meeting, Eric Brown, a microbiologist with the US Food and Drug Administration, explained that the FDA has been exploring the use of Roche 454 sequencing to characterize Salmonella isolates and to find markers for tracing outbreak strains back to their source.
And in Canada, the NML's Gilmour was lead author on a paper appearing in BMC Genomics this February in which researchers used the Roche 454 GS FLX platform to sequence the genomes of two L. monocytogenes strains isolated during a 2008 outbreak of listeriosis in Canada that killed 22 people and caused serious illness in dozens more.
"This study confirms that the latest generation of DNA sequencing technologies can be applied during high priority public health events," Gilmour and his co-authors wrote, "and laboratories need to prepare for this inevitability and assess how to properly analyze and interpret whole-genome sequences in the context of epidemiology."
Even so, Gilmour said it will take time for whole-genome sequencing to become a standard traceback method — largely due to remaining bioinformatics challenges.
"It's our job to learn how to use those [sequencing] technologies and glean the interesting information or the informative information," Gilmour said. "That's kind of the bottleneck we're at right now, is developing those bioinformatics tools to take that raw data and quickly parse through it and find relevant information."

There is still a long way before genome-sequencing or methods developed based on sequencing results will be standardized and incorporated into practice, but the results look promising and are opening new horizons for health applications.

References

Ward TJ, Evans P, Wiedmann M, Usgaard T, Roof SE, Stroika SG, & Hise K (2010). Molecular and phenotypic characterization of Listeria monocytogenes from U.S. Department of Agriculture Food Safety and Inspection Service surveillance of ready-to-eat foods and processing facilities. Journal of food protection, 73 (5), 861-9 PMID: 20501037

Van Stelten A, Simpson JM, Ward TJ, & Nightingale KK (2010). Revelation by single-nucleotide polymorphism genotyping that mutations leading to a premature stop codon in inlA are common among Listeria monocytogenes isolates from ready-to-eat foods but not human listeriosis cases. Applied and environmental microbiology, 76 (9), 2783-90 PMID: 20208021

St-Gelais D, Lessard J, Champagne CP, & Vuillemard JC (2009). Production of fresh Cheddar cheese curds with controlled postacidification and enhanced flavor. Journal of dairy science, 92 (5), 1856-63 PMID: 19389943

Rossetti L, Fornasari ME, Gatti M, Lazzi C, Neviani E, Giraffa G. (2008). Grana Padano cheese whey starters: microbial composition and strain distribution. Int J Food Microbiol. 2008 Sep 30;127(1-2):168-71. Epub 2008 Jun 12.PMID: 18620769

Flórez AB, Mayo B. (2006) Microbial diversity and succession during the manufacture and ripening of traditional, Spanish, blue-veined Cabrales cheese, as determined by PCR-DGGE. Int J Food Microbiol. 2006 Jul 15;110(2):165-71. Epub 2006 Jun 27.PMID: 16806553

Aurametrix is developing next-generation diagnostic tools for Personal Health Management. Better solutions for a healthier world

Microbes and Us

Microbes and us from Aurametrix, Live on Vokle, February 12, 2010 

Image via Wikipedia

Who's the True You? A human or a habitat for microbial communities?

Immediately after birth, every macroscopic creature is colonized by myriads of micro-critters that outnumber cells comprising the host.

Guts, ears, nose, skin, mouth, vagina, all environmentally exposed surfaces are home to thousands of species of bacteria, protists, algae, fungi (including yeast, molds, etc) and viruses. The types of microbes vary systematically across body habitats and time, as well as geographical location. Each finger tip is likely to have a distinct set of residents, so are left and right palms. If you are a woman, the number of populating you species is even larger.

Known as microbiota, the trillions of bacteria and other microorganisms could be our little friends. Some of them, dubbed probiotics, help to metabolize calories , provide nutrients, even shape immune responses during health and disease. A common gut bacteria called Bacteroides fragilis alleviates inflammation by restoring a balance of immune cells. It was shown to prevent inflammatory bowel disease in mice. Other bacteria shown to be protective in inflammatory bowel disease includes Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Lactobacillus acidophilus, Lactobacillus delbrueckii subspecies bulgaricus, Lactobacillus rhamnosus GG, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Escherichia coli Nissle 1917, Streptococcus salivarius subspecies thermophilus, Bacteriodes thetaiotaomicron, Faecalibacterium prausnitzii, etc.

Many other diseases called autoimmune strike when the immune system gets out of balance. Perhaps some microorganisms could protect us not only from IBD but also from disorders such as asthma, type-1 diabetes, or multiple sclerosis (incidence of which increased more than 3 times in the past years).

Humans are much more similar to one another at the level of the genome than the microbiome. Microbial ratios change with an individual's weight, travels, medications, stress, diet. For early men, changes in bacterial ratios favoring increased fat/energy storage was beneficial - as the periods when food was plentiful would be always followed by times when food is scarce. For a modern man, this is a potential health hazard rather than an advantage.

The most abundant bacterial groups detected by molecular screening are Bacteroides (relatively stable population profile) and the bacteria belonging to the Clostridium coccoides group and the Clostridium leptum group (see this article on the Normal Bacterial Flora of Humans).

A lower proportion of gram-positive anaerobes related to Faecalibacterium prausnitzii, Ruminococcus flavefaciens-Ruminococcus bromii, Eubacterium rectale-Clostridium coccoides, and Eubacterium cylindroides. The most widely promoted prebiotics inulin and fructooligosaccharides (neither is absorbed in the upper gastrointestinal tract) have been suggested to increase the number of bifidobacteria. Dahlia inulin was shown to cause a pronounced increase in the number of bacteria related to R. flavefaciens-R. bromii and E. cylindroides.

Other findings suggest that heavier individuals may have a different makeup of gut bugs than thin ones. The gut microbiota of obese mice has been shown to have significantly more of one main type of bacteria called Firmicutes and fewer of another kind called Bacteroidetes (both types populate human guts as well); in normal mice, the distribution is the opposite.
Whether you call them thongs, flip-flops or jandals, the simple rubber sandals could be a breeding ground for bacteria too. They allow easy access to oxygen, skin cells and oils, dirt and moisture. Eighty per cent of the population already have Staphylococcus aureus - found on sandals after being work for 4 days - on their skin, in their nose and armpits, yet this microbe aureus could make you pretty sick if it gets into a cut and into your blood, and if your immune system is not robust.
Some of bad bacteria can be even found in bottled water or in Fast Food Soda Fountains (see this article published in International Journal of Food Microbiology). 48% of soda fountains at fast food restaurants contain coliform bacteria. More than 11% of the beverages analyzed contained Escherichia coli and over 17% contained Chryseobacterium meningosepticum. Other opportunistic pathogenic microorganisms isolated from the beverages included species of Klebsiella, Staphylococcus, Stenotrophomonas, Candida, and Serratia.

Bacterial phylotypes Clostridium cocleatum, Clostridium thermosuccinogenes, Coprobacillus catenaformis, Ruminococcus bromii-like, Ruminococcus torques and R. torques were detected in similar amounts in IBS-C and IBS-D patients. C. thermosuccinogenes, however, was quantified in significantly different quantities depending on constipation or diarrhea-predominant cases. Bacteria similar to R. torques was more prevalent in IBS-D patients' intestinal microbiota than in that of control subjects. a R. bromii-like phylotype was associated with IBS-C patients. These findings further emphasized the possible contribution of the gastrointestinal microbiota in IBS. For IBD, novel invasive species of Escherichia coli possibly replacing some Clostridiales were found in inflamed mucosa. The number of E.coli correlated with the severity of Crohn's disease involving the ileum.

Differences in microbiota may depend on genetics, metabolism, environmental exposures during childhood, state of health. Selective increase in novel invasive species of E.coli seems to be involved in the etiopathogenesis to Crohn's disease involving the ileum (different species are implicated in UC). Other bacterial species specific to Crohn's are B. ovatus and B. vulgatus.

Myalgic Encephalomyelitis/Encephalopathy/Chronic Fatique Syndrome may be another condition caused by microbes. People with Cystic Fibrosis, for example, have more microbes enriched in aromatic amino acid metabolism in their airways. Note that this disease causes a distinct acidic breath - the more severe the condition is in an individual, the more acidic his breath becomes. The microbes were especially sensitive to amino-acid starvation indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota.

Altered breath resulting from changed micrflora is a known phenomenon and it can be detected not only by complex mass spec machines, but also by devices used in QA testing of foods (e.g. Cyranose pick up the scent of penzane, isoprene acetone, and benzene in the breath of lung cancer patients) and car air quality sensors to study human "fermentome". Hydrogen Sulfide Urine Test was developed (Kenny de Meirleir's work on testing was never published in a Peer Reviewed Journal) and is available for at-home use. Some people, however, prefer to use their nose instead of spending money for testing kits. Candida overgrowth usually is not associated with excess hydrogen sulfide. Biomed diagnostics offers inexpensive tests for Candida species.

Their InTray^TM Colorex^TM Screen also detects E.coli, Proteus mirabilis, Enterococcus sp., Klebsiella pneumnaiae, Staphylococcus aureus bacteria and Dermatophytes fungi. Many tests are available for urinary tract infections and various metabolites in urine. See also ongoing clinical trials on chemicals in human breath for diagnostics of diseases. The science of Grossology has only just scratched the surface of all the possibilities.

So, even seemingly innocent gut bacteria may be affecting many aspects of health and behavior. One day we may be even allowed to say: I’m sorry, sir, my microbes made me do it.

Even though the vast majority of our microbes are good for us or can be even used for diagnostics of the processes in our bodies, some are there to get us, contributing to skin diseases, body odor, malabsorption, gastrointestinal problems, ear infections and more.

Almost anything we touch or wear could be a breeding ground for bacteria. Remember the heavily reblogged and retwitted statement: "Wearing headphones for just an hour will increase the bacteria in your ear by 700 times"? Well, not exactly 700 times, 11 times and these are mostly our own bacteria that liked heat and humidity created in the ears and started to multiply more actively, but pretty much anything you stick in your ears - stethoscopes, hearing aids, audiological gear - comes out covered in microbes.

Parade beads could be be contaminated with bacteria too. Gasparilla beads, were shown to be covered with several types of bacteria includinf E. coli and salmonella.

Even cigarettes - besides their harmful toxic chemicals - host a bacterial bonanza —hundreds of different germs, including those responsible for many human illnesses, according to a new study. For example, Campylobacter, which can cause food poisoning and Guillain-Barre Syndrome; Clostridium, which causes food poisoning and pneumonias; Corynebacterium, also associated with pneumonias and other diseases; E. coli; Klebsiella, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, all of which are associated not only with pneumonia but also with urinary tract infections; and a number of Staphylococcus species that underlie the most common and serious hospital-associated infections.

Anoter source of pathogens is undercooked and spoiled food. Take pork, for example. Five out of 90 samples of retail pork in Lousiana tested positive for MRSA — an antibiotic-resistant staph infection — thanks to antibiotics piglet's ears. MRSA (pronounced “mersa”) stands for methicillin-resistant Staphylococcus aureus whose new strain ST398 is on the rise.

And of course, people could also pass microbes to each other: Epstein-Barr virus (EBV) (causing mononucleosis - infamously known as the kissing disease), Herpes Simplex Virus-1 (causing cold sores) bacterium Streptococcus (causing various infections such as gum disease and strep throat), H.pylori, Candida or other yeast species, Hepatitis B Virus and cytomegalovirus (CMV) are spread via oral transmission from microbe-containing saliva.

How can we control populations of microbes colonizing us? Besides drugs wiping out entire populations - assuming they are not resistant to these drugs, food could help in cultivation efforts too. Example: vinegar. It was shown to reduce counts of not-so-benefitial bacteria. Diluted solutions of various household sanitizers (apple cider vinegar, white vinegar, bleach, and a reconstituted lemon juice product) were tested for their effectiveness in reducing counts of inoculated Escherichia coli and naturally present aerobic, mesophilic bacteria on lettuce. Of the sanitizers tested, 35% white vinegar (1.9% acetic acid) was the most effective in reducing E. coli and other aerobic microbes.

Aurametrix is developing decision support systems to help you evaluate health risks, decide on preventative measures, estimate cost/benefits of performing diagnostic tests, determine your nutrition needs and life style adjustments. Better solutions for a healthier world.

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Human Body: A map of where Bacteria live

Who's The True You? A collaboration of our body and 100 trillion of microbes (bacteria, algae, yeast, protists and more) colonizing it.

Microbiota is specific to every individual, and varies systematically across body habitats and time, as well as geographical location, preventing or causing a disease after exposures to infectious agents.

Some human skin locations harbor even more diverse bacterial communities than the gut that we were thoughtfully nourishing with probiotics.

New analysis published in Science Express adds more information to the earlier results (from May 2009, for example), showing how diverse the microbiota is and how easy it is to re-colonize the skin.

We mapped some of the findings as shown in the Figure (on the right; the figure on the left maps bacteria in GI tract, from Dr. Richard Lord’s presentation at the 2008 Functional Medicine Symposium in Carlsbad, CA). Moist sites are shown with blue arrows, such as inside the nose, the armpits, the navel, dry areas are shown with green arrows, such as the forearm and oily sites are shown with yellow arrows: inside the ear, between the eyebrows, forehead, the back of the scalp.
Sites of most bacterial diversity were : The index finger, back of knee, forearm, palm and sole of foot.The forehead displayed the least diversity (with bacterial populations strongly preffering this site and not letting other bacteria to co-habit the space), but there were individual differences between different people. The mouth cavity showed the least variation in diversity both within individuals and between people. Studies of other microbes such as viruses and bacteriophages show low diversity in the airways as well, even though the human respiratory tract is constantly exposed to a wide variety of microbes and environmental agents. There is a difference between diseased and non-diseased individuals though - in Cystic Fibrosis (CF). for example, viromes are enriched in aromatic amino acid metabolism. Note that this disease causes a distinct acidic breath - the more severe the condition is in an individual, the more acidic his breath becomes. The microbes were especially sensitive to amino-acid starvation indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota.
Altered breath resulting from changed micrflora is a known phenomenon and it can be detected not only by complex mass spec machines, but also by devices used in QA testing of foods (e.g. Cyranose pick up the scent of penzane, isoprene acetone, and benzene in the breath of lung cancer patients) and car air quality sensors to study human "fermentome". (See also ongoing clinical trials on chemicals in human breath for diagnostics of diseases).

Altered bacterial populations could, indeed, be studied by metabonomic profiling. At present, however, the most accurate analysis, was performed based on microbial DNA or 16S RNA.
The study subjects were sampled four times each over a three-month period, typically after showering an hour or two earlier. Microbial DNA was then isolated directly from swabs used for sampling each body site. To recover bacteria from the skin surface, it was enough to swab it once by a wet cotton swab in 30s.

Microbes we live with

Mirrored from Aurametrix

Just a few hours after birth, every human being is colonized by more microbes than there are cells in the body. We are home to thousands of species of bacteria, protists, algae, fungi, molds and viruses.

Some of these microbes help us to develop blood vessels in the gut, digest our food and train our immune system. Others make us sick, contributing to skin diseases, body odor, malabsorption, gastrointestinal problems, ear infections and more. Some of such bacteria can be even found in bottled water.

The composition and distribution of microbial populations depend on the age, diet, fitness, genetics, hygiene, and overall state of health of their hosts.

Dr. Bonnie Bassler, of Princeton University, gives an estimate of how many bacteria live on us in her Ted talk, at the 2009 TED Conference. Number of human cells in the average adult = 1 trillion. Number of bacteria cells in association with the average adult = 10 trillion. Even more intriguing, is the number of genes that humans have is about 30,000. How many different bacteria genes are associated with us? 300,000! So, are we human or are we bacteria?

Aurametrix has one the most complete databases of species found on human body and in human food.

Check these sites for more info on our little companions:

• The Normal Bacterial Flora of Humans

• Alphabetical List of Pathogenic Bacteria Ver.1.2 by Pathogenic Bacteria Database
  

[A][B][C][D][E][F][G][H][I][J][K][L][M][N][O][P][Q][R][S][T][U][V][W][X][Y][Z]

• IMG Genomes

finished/draft		Total
Bacteria	781/503	1284
Archaea	56/3	59
Eukarya	19/30	49
Plasmids	974/0	974
Viruses	2524/0	2524
All Genomes	4354/536	4890
Genome by Metadata
IMG Statistics
Project Map
Content History

• The NCBI Taxonomy Database

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• Living With Germs: On Infectious Diseases (oup.com)
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