More "Bugs R Us": gut, mouth and skin edition

I recently mentioned the article in The Economist which detailed the growing realisation in biology that humans (and all animals I guess) are best viewed as ecosystems, given the incredibly diverse and important role the bacteria that live in and on us play in health and illness.

Since then, there have been a few things about bacteria and health that have come to my attention:

Gut:   Four Corners had a fascinating documentary about the research indicating that at least some types of autism are related to harmful intestinal bacteria.  Unfortunately, the particular strain that they were talking about appears to be very difficult to remove permanently with antibiotics.

Although this idea appears to be catching on only slowly in the medical community, it was hard not to be impressed with the video apparently showing the difference the antibiotic treatment made to the behaviour in the young kid who had been treated for a while a decade or so ago.  (He's now 19 and still suffers autism, but had to stop the antibiotics since they just can't be taken forever.) 

I don't think they mentioned it, but I wondered whether anyone had thought about trying the icky but apparently effective idea of "fecal transplant" as a way of getting rid of the unwanted bacteria in autistic kids.  Googling the topic, I see that indeed this is an area of interest.  The Atlantic had a recent article about people wanting to do "at home" fecal implants (!)  Only with doctor's guidance, I would suggest.

Mouth:   In the Australian forum for wingnuts (and those who like to tell them they are wrong) that starts with the letter "C", I recently noted that I assumed that the differences in mouth bacteria might account (in large part) for why some people just seem to be more susceptible to cavities, despite having relatively low sugar diets and normal dental hygiene.

I had likely forgotten that I had read something about this years ago, as the topic does get a brief mention in an article in Scientific American in 2002:

All bacterial biofilms are not alike, however. Although Mutans streptococci and other species have been implicated as primary culprits in causing caries, some people who are infected with these species of bugs don¿t get cavities. Genotypically different strains of the same bugs exhibit varying levels of cariogenicity. Therefore, it¿s not just the quantity of plaque biofilm present, but the specific strain with which one is infected that is important in predicting who might get cavities.

 This is obviously an area of ongoing research, and this abstract of a 2009 Japanese paper indicates the situation is complex:

Recent analyses with ribosomal RNA-based technologies have revealed the diversity of bacterial populations within dental biofilms, and have highlighted their important contributions to oral health and disease. Dental biofilms are exceedingly complex and multispecies ecosystems, where oral bacteria interact cooperatively or competitively with other members. Bacterial interactions that influence dental biofilm communities include various different mechanisms. During the early stage of biofilm formation, it is known that planktonic bacterial cells directly attach to surfaces of the oral cavity or indirectly bind to other bacterial cells that have already colonized. Adherence through co-aggregation may be critical for the temporary retention of bacteria on dental surfaces, and may facilitate eventual bacterial colonization. It is likely that metabolic communication, genetic exchange, production of inhibitory factors (e.g., bacteriocins, hydrogen peroxide, etc.), and quorum-sensing are pivotal regulatory factors that determine the bacterial composition and/or metabolism. Since each bacterium can easily access a neighboring bacterial cell and its metabolites, genetic exchanges and metabolic communication may occur frequently in dental biofilms.

Most interestingly, while Googling this, I also stumble across the ongoing efforts of a Florida company Oragenics to prevent cavities by introducing genetically modified mouth bacteria to out compete the harmful ones:

 Our replacement therapy technology is based on the creation of a genetically altered strain of S. mutans, called SMaRT, which does not produce lactic acid. Our SMaRT strain is engineered to have a selective colonization advantage over native S. mutans strains in that SMaRT produces minute amounts of a lantibiotic that kills off the native strains but leaves the SMaRT strain unharmed. Thus SMaRT Replacement Therapy can permanently replace native lactic acid-producing strains of S. mutans in the oral cavity, thereby potentially providing lifelong protection against the primary cause of tooth decay. The SMaRT strain has been extensively and successfully tested for safety and efficacy in laboratory and animal models.

SMaRT Replacement Therapy is designed to be applied topically to the teeth by a dentist, pediatrician or primary care physician during a routine office visit. A suspension of the SMaRT strain is administered using a cotton-tipped swab during a single five-minute, pain-free treatment. Following treatment, the SMaRT strain should displace the native, decay-causing S. mutans strains over a six to twelve month period and permanently occupy the niche on the tooth surfaces normally occupied by native S. mutans.

Their website goes on to explain that trials have been done on animals (presumably successfully) but FDA requirements for human trials have been tricky:

 After we submitted additional information, the FDA issued a clinical hold letter in June 2007 for the proposed trial with the attenuated strain, citing the need for a plan with respect to serious adverse effects; a plan for the eradication of the attenuated strain in trial subjects’ offspring; and a required pregnancy test for female partners of subjects. We submitted additional protocols in response to the FDA’s concerns. In August 2007, the FDA issued a clinical hold letter with required revisions to the protocol for offspring of subjects. We submitted a response to the clinical hold letter in September 2007, and the FDA removed the clinical hold for our Phase 1 trial in the attenuated strain in October 2007.

We are in the process of commencing a second Phase 1 clinical trial of an attenuated version of our SMaRT Replacement Therapy, which will examine the safety and genetic stability of the SMaRT strain during administration to ten healthy adult male subjects over a two-week period. As a precautionary measure, this trial will use an attenuated version of the SMaRT strain that is dependent on D-alanine, which is a specific amino acid not normally found in the human diet. D-Alanine will be administered though a mouthwash provided to the patient group, and must be administered daily or the attenuated strain will perish in the oral cavity. We expect the second Phase 1 clinical trial of the attenuated strain, including a three-month follow-up examination of subjects, to be concluded in 2011. If the second Phase 1 trial of the attenuated strain is successful and if the FDA lifts the clinical hold on the IND for the non-attenuated version of the SMaRT strain, we anticipate that we would conduct a third Phase 1 trial using the non-attenuated SMaRT strain instead of the attenuated version.

All rather complicated, but it sounds as if we might be hearing soon about whether it works in humans, or not.

Skin:  There was also news this week that the adult red faced skin condition rosacea may be caused by the bacteria that live in the face mites that quietly live in the pores of many faces.   (My January 2011 post which featured a photo of them and had the catchy title "The bugs, they're all over me!" remains one of the more commonly Googled way that people arrive at this blog.) 

This would seem to provide a good explanation as to why rosacea usually responds to antibiotics, as  it seems no one had previously quite understood why.  It was known that people with rosacea usually had higher numbers of face mites than other people, and sometimes success has been had with trying to kill the mites directly.

The last bizarre part of this biological story is that face mites apparently don't have an anus (see, I avoided trying to work out the plural for "anus") so the gut bacteria in them don't get out until the mite dies.  But when they do, they cause an immune reaction that causes inflammation and redness.


Truly, it seems that bacteria rule.

And finally:   you know what my mind always wanders to when reading about these topics?   George Lucas and his bizarre sounding introduction of "midi-chlorians" as being behind The Force:

Without the midi-chlorians, life could not exist, and we would have no knowledge of the Force. They continually speak to us, telling us the will of the Force. When you learn to quiet your mind, you'll hear them speaking to you."

―Qui-Gon Jinn, to Anakin Skywalker

Obviously (and confirmed by Lucas) based on mitochondria, this seemed a really weird way to give a materialistic explanation for The Force.   But, the more I read about the importance of bacteria, the more I worry that Lucas might be the accidental Einstein of biology.