Long-term benefits: Negotiating with bacteria

     I vividly remember in grade school  seeing a movie about the war that goes on in our bodies between our immune system and bacteria. The white blood cells were like knights on their white horses and the invading bacteria were like insects. This was about the time Penicillin was first being widely used after WW II. The warfare metaphor was not new—we have been looking for "magic bullets" to treat syphilis ever since the germ theory was accepted. The concept of antibacterial warfare has dominated our thinking in dealing with bacteria. We now have bigger and better weapons, but the enemy bacteria are very adept at learning how to cope with them; most of them are resistant to Penicillin. And, thanks to earlier use in animals than in humans, many bacteria are resistant to our new antibiotics by the time they are available to us. It is a very real arms race that brings us now to the  fear of bacteria resistant to all of our antibiotics. If we look at the odds in this war we have further indication for concern. 95% of the bacteria that existed 1.7 billion years ago, when the first cell appeared, are still around, but 95% of the "higher" organisms, developed since that time, are now extinct. We need other options in this warfare. For a further look at some interesting parallels between our warfare with bacteria and with our fellow men click here. 

We need to consider a much broader perspective as we engage this enemy. 

• Bacteria began around three-and-a-half billion years ago. They were the only living things on this earth for almost two billion years. 

• During this period of time they learned to use the sun's energy, liberate and use oxygen, and ferment other bacteria. 

• They reached a balance and learned to live in co-operation with each other. 

• Not having much interest in intellectual property rights they even learned how to share information with each other by sharing genetic material.  

  • They do this and mutate much more actively when they are under stress, like when we use antibiotics to kill them.  

  • This is the main reason we are always playing catch-up with antibiotics.  

  • We are also trying to use bacteria, the unquestionable experts at slipping genes to others, to put corrected genes into people with genetic diseases—but the people keep dying from the infection that we introduce.  

Evolutionary biologists looking at the archeological record of these bacteria point out that the first nucleated cell combined all of the abilities of the various bacteria into one cell. 

• Evolution, according to these biologists, is not "red in tooth and claw," as described by early evolutionists, but a triumph of co-operation. 

• These biologist include scholars like Lynn Marguilis, whose book, Early Life, portrays the developments of our earth's history over a billion years ago.

•   Elisabet Sahtouris, another of these biologists, points out that the new concept of the evolutionary cycle is a progression: from unity, to diversity, to conflict, to negotiation, to resolution, to co-operation, and to a new and more highly developed unity.

    While this line of reasoning is not generally accepted by most biologists who continue to look at random mutation and its environmental success as the fundamental principle of evolution. It does provide a more friendly answer to the questions brought up by some about the complexity of some biologic processes, like blood clotting, that rely on the cascade of processes that individually do not seem to have any survival advantage. Without the whole cascade each of the mutations leading to the individual steps would have been meaningless and without advantage. If they can be seen as the result of co-operation the end result makes more sense. 

Paul Ewald is a biologist who has written  on the subject of how bacteria evolve (Evolution of Infectious Disease and  Plague Time). 

• His main argument is that when bacteria can move easily from one person to another they become more virulent—they cause more, as well as more serious, infections. 

• Conversely when we clean up our water, or use mosquito netting, or condoms—that block the spread of the virus or bacteria—they become less virulent.  

• In the section on glycobiology I wrote about how the sugar complexes on the cells provide a means of attachment for bacteria. 

Using soluble sugars to prevent bacterial adherence inside the body promotes the same evolutionary pressures as the barriers described by Ewald.  

• We saw earlier how this happened with the women who drank the cranberry lingonberry juice extract. They had less infections. 

• The most likely reason is a change in the nature of their bacteria. Making it harder for the bacteria to hold on selects for bacteria that hold on by a different method and do not cause infections. 

Nathan Sharon, the pioneer of this aspect of infectious disease, points out that the sugars on cell surfaces can change and that when they do they can provide a means of communication: between our cells, between our cells and bacteria, and between bacteria.

•  Not only do our body's cells talk to their neighbors and move in our bodies to places where they are needed, but bacteria are able to talk to the host cells in their environment and promote changes, either helpful or harmful, in those cells.

•  And when bacteria get together, they talk among themselves by releasing chemicals in a process called quorum sensing. 

• As more bacteria release these chemicals the bacteria reach a point where they change their focus. 

• One of the things some bacteria do when they have been allowed sufficient time to grow is to make a biofilm. 

• These are essentially houses in which the bacteria live that are sometimes as elaborate on a bacterial scale as the skyline of New York.  

• When bacteria get to this stage it is difficult to get rid of them because the antibiotics can't get into their houses. 

  • Dental plaque is a biofilm and we have to go to the dentist to get this biofilm scraped off. 

  • Frequent exposure to xylitol also removes plaque. 

  • Recent studies suggest that some cases of recurrent ear infections occur because of biofilm formation. 

  • Unfortunately we can't scrape off the biofilm in the back of the nose. 

Clearly we need to interrupt this bacterial communication if we wish to stop the problems. We have already seen how xylitol blocks adherence. And, following Ewald's ideas we should see bacteria that are less virulent when repeatedly exposed to xylitol.

• Of course we can't ask the bacteria if they understand and agree with what we want—we have to see whether or not they are changed by looking at what they do. 

• And the changes need to be long-term, just as they were with the urinary infections.

What xylitol says to the bacteria.

• In the early 1990’s a study, performed by dentists at the University of Michigan, was carried out in Belize to look at the effect of xylitol on tooth decay in children at the time they lose their primary teeth. 

  • Belize is a good place for such a study because they grow lots of sugar cane. 

  • The children there often chew it like candy and this results in lots of cavities.

• The study lasted for two years and used six different kinds of gum, including mixes of xylitol, sorbitol, and maltitol as well as gums with only one sweetener.

  •  The children chewed two sticks of this gum at regular intervals four times a day and were given sufficient for the weekend on Friday. 

  • At the end of the two years they found that 100% xylitol was the best of the six types of gum used in the study. 

  • This did not surprise anyone because that is what they found with all of the other studies with the gum.

• But five years later dental researchers from the University of Washington returned and looked at the children again. They found that if the children started the regular program of xylitol gum-chewing one to two years before their permanent teeth erupted, then five years after the end of the study, with no xylitol during the five years, they had 90% fewer cavities than the control group.

Beside the spectacular benefit of this treatment the question it raises is how this long-term benefit occurs. Bacterial indigestion and reduced adherence are local and short-term effects of xylitol; they cannot explain this observed long-term benefit. Like the study with the cranberry-lingonberry extract this long-term benefit is only explained by changes in either the nature of the bacteria or the type of bacteria. 

• Luc Trahan, the Canadian researcher, had published his studies three years earlier showing that the nature of S. mutans changed when exposed to xylitol.

• In March 2000, Eva Soderling reported the findings of her group that was looking at the effect of maternal xylitol gum chewing on the S. Mutans carrier status of their children. 

  • For the first two years after giving birth these women either chewed xylitol gum, or had treatments every six months with fluoride or chlorhexidine.

  •  None of the treatments changed the S. Mutans carriage in the mothers, but less than 10% of the children whose mothers chewed the xylitol gum carried S. Mutans at age two. 

  • They had other bacteria that did not cause tooth decay – the type of bacteria changed.  

  • The numbers were three and five times less respectively than those treated with chlorhexidine or fluoride varnish. 

  • The latest follow up on these children shows that at five years they have 70% fewer cavities than the other groups. 

  • The correlation of the benefit seen in the Belize children with the loss of their primary teeth also argues for a change in the type of bacteria.

•  A recent study from the University of Washington Dental School, that had done the follow-up study in Belize, looked at what happens to the bacteria on our teeth in the presence of xylitol. 

  • They used adults, so they did not get the benefit of changing out your teeth seen in the Belize children, and found that their bacteria became tolerant of xylitol in the manner Luc Trahan pointed out. 

  • And that this tolerance was accompanied with not causing tooth decay.

• While decay causing bacteria are important we need to remember that all of the studies comparing S. mutans, that cause tooth decay, and S. pneumoniae, that cause most ear, sinus, and bronchial infections, show them equally effected by xylitol. Obviously more studies need to be done, but they will not be funded until enough people clean their noses regularly and show the government and the health care industry just how effective regularly cleaning the nose is at reducing associated problems. 

• Don't hold your breath for this to happen because preventing problems is not in the financial interest of the health care industry. More about the roots of our health care problems is available at Common Sense Medicine.

     We have been locked in the conflict stage too long and it is time to get on with negotiating. The long-term effects of cranberry juice extract and xylitol—the fact that xylitol changes the nature of the bacteria as described by Trahan and reduces the carrier state in the community, without killing the bacteria—together with the communicative function of these sugars opens the door to the possibility of negotiation in this biological arms race. Ewald closes The Evolution of Infectious Disease with the hope that we can "domesticate" the bacteria and get out of the arms race we are losing. I think this possibility and the use of simple food sugars to facilitate it is one of the most exciting developments in infectious disease since the discovery of antibiotics. It is, however, a lot easier to wage war than it is to make peace. Making peace means talking, even when you are not sure the other person is listening. Two years of gum chewing, and losing their primary teeth where the plaque was home to the harmful bacteria, was necessary to convince the bacteria in these children’s mouths to behave differently or just to not make their home there. It is a lot more effort than just sending off a smart bomb to blow them up, but smart bombs are just another challenge for bacteria. Again feeding our enemies is an infrequently used option,  but 35 generations, the time it takes to change a wolf to a dog, is a few days for rapidly multiplying bacteria. 

* * * * * * * * * * * * *

In summary, xylitol has two short-term actions, indigestion and decreased adherence, on several bacteria—that live in the mouth and cause tooth decay, and in the nose that cause upper respiratory infections. In addition xylitol has long-term effects on S.Mutans that change it to being more friendly (less virulent) and reduces the number of people in the community who have the bacteria. And it does this without killing the bacteria, most likely by filling the receptor sites on the bacteria whose function it is to communicate with the environment, i.e.  by negotiating. What it seems to say to the bacteria is "shape up or ship out." Whether these long-term effects will hold on the bacteria living in the nose will have to be determined when enough people use it regularly in the nose. My own experience over the past four years suggests it does.

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References:

[The first three references pertain to mannose and bladder infections.]

 

Antimicrob Agents Chemother 1989 Jan;33(1):92-8

Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells.

Zafriri D, Ofek I, Adar R, Pocino M, Sharon N

Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.

Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.

PMID: 2653218

Nippon Hinyokika Gakkai Zasshi 1989 Dec;80(12):1816-23

[Anti-bacterial defense mechanism of the urinary bladder. Role of mannose in urine].

[Article in Japanese]

Toyota S, Fukushi Y, Katoh S, Orikasa S, Suzuki Y

Bacterial adherence to mucosa is thought to be an initial and important stage to cause urinary tract infection. Among some mechanisms of bacterial adherence, the role of fimbriae and its receptor is worthy of notice. In particular, type 1 fimbriae, for which mannose is assumed as a receptor, is reported as the most common type and called "common fimbriae". Therefore if a certain amount of mannose is present in urine, it will cover the fimbriae of bacteria and competitively block the bacterial adherence to bladder mucosa. As the first step, we tried to detect mannose in urine by high performance liquid chromatography (HPLC). Sugar can be measured by detecting the fluorescence which is produced by a sugar separated by ion exchange, reacting with arginine at high temperature. The results using standard sugar samples should have highly stable retention time and concentration curve with the minimum detectable mannose concentration of 0.02 microgram. We investigated mannose in urine from 186 cases. Since the mannose peak was often masked by near unidentified peaks, the peak of mannose could be detected only in 80 cases and its concentration could be measured only in 24 cases. Mannose concentration in the urine of the 24 cases was between 2.6 and 108.7 micrograms/ml and in most of cases it was lower than 20 micrograms/ml. Secondary, we examined the possibility of a mannose in urine to prevent bacterial adherence to mucosa by the hemagglutination test using guinea pig erythrocytes and type 1 fimbriated E. coli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 2576290, UI: 90172805

        [See also Dr. Jonathan Wright's article on mannose and urinary tract infections online at http://www.tahoma-clinic.com/mannose.shtml  ]

Following two articles deal with biofilms:

Nippon Jibiinkoka Gakkai Kaiho 1998 Jan;101(1):25-36

[Inhibitory effect of macrolide antibiotics on biofilm formation by Pseudomonas aeruginosa].

[Article in Japanese]

Kondoh K, Hashiba M

Department of Otorhinolaryngology, Nagoya City University Medical School.

In recent years, various medical indwelling devices have been developed and used. Bacteria adhering to these devices often cause refractory infection. In the field of otolaryngology, refractory infection accompanying these medical indwelling devices such as middle ear ventilation tubes and artificial auditory ossicles has been reported. The concept of bacterial biofilm infection has been suggested as an explanation for the refractory infection. Furthermore it has been reported that a bacterial biofilm is involved in refractory infection unrelated to medical indwelling devices. Topical biofilm formation was detected in patients with chronic sinusitis, chronic purulent otitis media or habitual tonsillitis. In this study, we morphologically and quantitatively examined the biofilm-forming capacity of a clinically isolated strain of mucoid type Psecudomonas aeruginosa on Teflon to investigate the effects of macrolide antibiotics on bacterial biofilm formation. In the morphological examination, P.aeruginosa was cultured together with a Teflon sheet in minimal medium containing various concentrations of the macrolide antibiotics clarithromycin (CAM), erythromycin (EM) and midecamycin (MDM), at 37 degrees C for 7 days. The surfaces of the Teflon sheets were examined by electron microscopy. The adherent bacteria and biofilm formation on Teflon sheets soaked in minimal medium containing CAM or EM were found to be decreased in a dose-dependent manner. However, in the Teflon sheets soaked in minimal medium containing MDM, there was no decrease in biofilm formation regardless of the MDM concentration. In the quantitative examination, P. aeruginosa was cultured in minimal medium containing various concentrations of the macrolide antibiotics at 37 degrees C for 7 days together with Teflon beads. The levels of hexose, protein and alginate adhering to the Telfon beads were quantified as an estimation of biofilm formation. On Teflon beads treated with CAM or EM, there were dose-dependent decreases in hexose, protein and alginate levels. In particular, marked decreases were noted when CAM and EM concentrations were 10 micrograms/ml or more. Furthermore, there was no significant difference between CAM and EM. However, in the presence of MDM, there was no decrease in hexose, protein or alginate levels regardless of the MDM concentration. The minimal inhibitory concentration (MIC100) of each macrolide against P. aeruginosa used in this experiment was 100 micrograms/ml or more. There may be no bactericidal effect on this strain at the macrolide concentrations used in this experiment. However, this experiment used 7-day treatment. The long-term bactericidal activity of macrolides was examined. In the presence of CAM or MDM, bacterial levels after culture were similar to preculture levels or slightly lower than the preculture levels. In the presence of EM, bacterial levels were similar to the preculture levels. These results demonstrated that CAM and EM, which are 14-membered macrolides inhibited biofilm formation, while MDM which is 16-membered macrolide, did not. These inhibitory effects of CAM and EM may be related to actions other than bactericidal activity. In our experiment, CAM and EM inhibited biofilm formation at 10 micrograms/ml or more. This concentration corresponded to 1/20 x MIC. This concentration can be achieved in tissues, nasal discharge and sputum with actual clinical doses. Therefore, these agents may be effective against biofilm disease caused by P. aeruginosa in the field of otolaryngology.

Evidence of bacterial metabolic activity in culture-negative otitis media with effusion.

Rayner MG, Zhang Y, Gorry MC, Chen Y, Post JC, Ehrlich GD

Department of Pathology, University of Pittsburgh School of Medicine, Pa, USA.

CONTEXT: Otitis media with effusion (OME) can lead to significant hearing loss in children. Although previous studies have shown that bacterial DNA is present in a significant percentage of effusions sterile by culture, whether the DNA represents viable organisms or "fossilized remains" is unknown. OBJECTIVE: To determine if bacterial messenger RNA (mRNA), as detected by a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay, is present in chronic pediatric middle ear effusions that contain bacterial DNA but are sterile by standard cultural methods. Bacterial mRNAs have a half-life measured in seconds to minutes; therefore, detection of bacteria-specific mRNAs would be evidence that metabolically active organisms are present. DESIGN: Blinded comparative study. PATIENTS: A total of 93 effusions from pediatric outpatients seen for myringotomy and tube placement for chronic (>3 months) OME (median age of children, 17 months). SETTING: Tertiary care pediatric hospital. MAIN OUTCOME MEASURES: Percentage of positive test results for RT-PCR-based assays compared with culture for Haemophilus influenzae and concordance between RT-PCR and PCR-based findings for bacterial nucleic acids. RESULTS: Eleven (11.8%) of the 93 specimens tested positive by culture, PCR, and RT-PCR for H influenzae. A total of 29 specimens (31.2%) were positive by PCR but negative by culture for H influenzae. All 29 specimens were positive by RT-PCR for H influenzae-specific mRNA. CONCLUSIONS: The RT-PCR-based assay system can detect the presence of bacterial mRNA in a significant percentage of culturally sterile middle ear effusions, establishing the presence of viable, metabolically active, intact organisms in some culture-negative OME.

Caries Res 1996;30(6):408-17

Polyol chewing gums and caries rates in primary dentition: a 24-month cohort study.
Makinen KK, Hujoel PP, Bennett CA, Isotupa KP, Makinen PL, Allen P
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, USA.

The effect of 2-year chewing-gum use on the caries rates of primary teeth was studied in a combined school and home program in a sample of 510 initially 6-year-old subjects with high caries experience, low availability of fluoride, and difficult access to dental care. The gum, formed into either sticks or pellets, comprised either xylitol, sorbitol, or mixtures thereof. The gum was chewed for 5 min under supervision five times a day during the school year, and for variable times during nonschool days. Seven groups were studied. One group received no gum; two xylitol gum groups received either pellet or stick gum as did, two sorbitol gum groups, and two groups received either of two types of xylitol/sorbitol pellet gum. The response variable was the development of a frank carious lesion detectable by physical loss of enamel and probable extension to the dentin for those surfaces of primary teeth that were not cavitated at baseline. Caries rates associated with the use of each of the gum types were compared to the caries rates in the no-gum group. The usage of all polyol gums resulted in a significant decrease of the caries onset rate (p < 0.05). The caries onset risk for a primary surface in the xylitol pellet and the sorbitol pellet groups was 35 and 44% of that in the no-gum group (relative risk, 0.35; 95% confidence interval, 0.21-0.59; relative risk, 0.44; 95% confidence interval, 0.30-0.63, respectively). The caries onset risk in the xylitol stick gum group was 53% of that in the no-gum group (relative risk, 0.53; 95% confidence interval, 0.39-0.72), which was marginally (p = 0.1520) lower than in the sorbitol stick gum group (relative risk, 0.70; 95% confidence interval, 0.52-0.94). The usage of both xylitol/sorbitol mixtures in pellet form was associated with a caries onset rate comparable with the usage of the xylitol stick gum. The largest caries risk reduction was observed in the group receiving xylitol pellet gum.

J Dent Res 1999 Mar;78(3):797-803

The optimum time to initiate habitual xylitol gum-chewing for obtaining long-term caries prevention. Hujoel PP, Makinen KK, Bennett CA, Isotupa KP, Isokangas PJ, Allen P, Makinen PL
Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle 98195, USA.

Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixtures provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing - those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewed gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixtures. There was a "no-gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk [RR], 0.65; 95% confidence interval [c.i.], 0.39 to 1.07; p < 0.18). Xylitol gum and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59% (RR, 0.41; 95% c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44% (RR, 0.56; 95% c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reductions of 93% (p < 0.0054) and 88% (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.

 

Emergence of multiple xylitol-resistant (fructose PTS-) mutants from human isolates of Mutans streptococci during growth on dietary sugars in the presence of xylitol.
Trahan L, Bourgeau G, Breton R
Groupe de Recherche en Ecologie Buccale, Faculte de medecine dentaire, Universite Laval, Quebec, Canada.

The growth inhibition of Mutans streptococci is one of the proposed mechanisms of action of xylitol, a caries-preventive natural carbohydrate sweetener. Xylitol is taken up and accumulated as non-metabolizable, toxic xylitol phosphate via a constitutive fructose PTS, and selects, during in vitro growth at the expense of glucose, for natural xylitol-resistant mutants that lack constitutive fructose PTS activity. Since long-term xylitol consumption leads to the emergence of xylitol-resistant Mutans populations in humans in an oral environment containing sugars of dietary origin, we wanted to test the hypothesis that xylitol-resistant cells could be selected from Mutans streptococci strains during in vitro growth on fructose, sucrose, or lactose. Three laboratory strains and three fresh Mutans streptococcal isolates were repeatedly transferred in trypticase-yeast extract medium supplemented with glucose, fructose, sucrose, or lactose in the presence and absence of xylitol. Depending on the growth sugar, the presence of xylitol resulted in the selection of xylitol-resistant populations for several of the six strains tested, but not necessarily in the presence of all four sugars. All six strains rapidly became xylitol-resistant when grown on glucose in the presence of xylitol. All three fresh isolates became xylitol-resistant after 9 to 16 transfers in the presence of fructose or sucrose plus xylitol, while none of the laboratory strains became xylitol-resistant after 16 transfers in the presence of these sugars. The growth rates of 12 xylitol-resistant mutants in the presence of eight sugars suggested the existence of various types of xylitol-resistant mutants. The data partially explain the occurrence of xylitol-resistant Mutans populations in long-term xylitol consumers and suggest a mechanism consistent with a selection process. Since various preliminary results suggest that xylitol-resistant natural mutants may be less virulent and less cariogenic than their parent strains, this selection process may alter, for the better, the Mutans streptococci population of the plaque and play a role in the caries-preventive action of xylitol.

J Dent Res 2000 Mar;79(3):882-7

Influence of maternal xylitol consumption on acquisition of Mutans streptococci by infants.

Soderling E, Isokangas P, Pienihakkinen K, Tenovuo J

Institute of Dentistry, University of Turku, Finland. eva.soderling@utu.fi

Xylitol is effective as a non-cariogenic sugar substitute. Habitual xylitol consumption appears to select for Mutans streptococci (MS) with impaired adhesion properties, i.e., they shed easily to saliva from plaque. One hundred sixty-nine mother-child pairs participated in a two-year study exploring whether the mothers' xylitol consumption could be used to prevent mother-child transmission of Mutans streptococci. All mothers showed high salivary levels of Mutans streptococci during pregnancy. The mothers in the xylitol group (n = 106) were requested to chew xylitol-sweetened gum (65% w/w) at least 2 or 3 times a day, starting three months after delivery. In the two control groups, the mothers received either chlorhexidine (n = 30) or fluoride (n = 33) varnish treatments at 6, 12, and 18 months after delivery. The children did not chew gum or receive varnish treatments. MS were assessed from the mothers' saliva at half-year intervals and from the children's plaque at the one- and two-year examinations. The MS were cultured on Mitis salivarius agars containing bacitracin. The salivary MS levels of the mothers remained high and not significantly different among the three study groups throughout the study. At two years of age, 9.7% of the children in the xylitol, 28.6% in the chlorhexidine, and 48.5% in the fluoride varnish group showed a detectable level of MS. In conclusion, therefore, habitual xylitol consumption by mothers was associated with a statistically significant reduction of the probability of mother-child transmission of MS assessed at two years of age. The effect was superior to that obtained with either chlorhexidine or fluoride varnish treatments performed as single applications at six-month intervals.

 

J Dent Res 2000 Nov;79(11):1885-9

Occurrence of dental decay in children after maternal consumption of xylitol chewing gum, a follow-up from 0 to 5 years of age.

Isokangas P, Soderling E, Pienihakkinen K, Alanen P

Ylivieska Health Care Center, University of Turku, Finland.

Studies have shown that prevention of mutans streptococci (MS) colonization in early childhood can lead to prevention of dental decay. In the microbiological part of the present study in Ylivieska, Finland, with 195 mothers with high salivary MS levels, regular maternal use of xylitol chewing gum resulted in a statistically significant reduction in MS colonization in their children's teeth at the age of 2 years compared with teeth in children whose mothers received fluoride or chlorhexidine varnish treatment. The children did not chew gum or receive varnish treatments. For the present study, the children were examined annually for caries occurrence by experienced clinicians who did not know whether the children were colonized with MS. Regardless of the maternal prevention group, the presence of MS colonization in children at the age of 2 years was significantly related to each child's age at the first caries attack in the primary dentition. In children at the age of 5 years, the dentinal caries (dmf) in the xylitol group was reduced by about 70% as compared with that in the fluoride or chlorhexidine group. We conclude that maternal use of xylitol chewing gum can prevent dental caries in their children by prohibiting the transmission of MS from mother to child.

 

BMJ 2001 Jun 30;322(7302):1571

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.

Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M.

Department of Pediatrics, University of Oulu, Oulu, Fin-90220, Finland.

Objective: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial. Setting: Health centres for university students and staff of university hospital. Participants: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. Results: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). Conclusion: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

 

Cell 2002 May 17;109(4):421-4

 
Small talk. Cell-to-cell communication in bacteria.

Bassler BL.

Department of Molecular Biology, Princeton University, NJ 08544, USA. bbassler@molbio.princeton.edu

In a process called quorum sensing, groups of bacteria communicate with one another to coordinate their behavior and function like a multicellular organism. A diverse array of secreted chemical signal molecules and signal detection apparatuses facilitate highly productive intra- and interspecies relationships.

 

Sci Am 1993 Jan;268(1):82-9

Erratum in:

• Sci Am 1993 Mar;268(3):12

Carbohydrates in cell recognition.

Sharon N, Lis H.

Biophysics Department, Weizmann Institute of Science, Rehovot, Israel.

Telltale surface sugars enable cells to identify and interact with one another. New drugs aimed at those carbohydrates could stop infection and inflammation.

 

N Engl J Med 1991 May 30;324(22):1599

Anti-Escherichia coli adhesin activity of cranberry and blueberry juices.

Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N.

 

J Am Dent Assoc 2002 Apr;133(4):435-41.

How xylitol-containing products affect cariogenic bacteria.

Roberts MC, Riedy CA, Coldwell SE, Nagahama S, Judge K, Lam M, Kaakko T, Castillo JL, Milgrom P.

Department of Pathobiology, University of Washington, Seattle, USA.

BACKGROUND: The authors examined the effect of xylitol, a naturally occurring sweetener, on levels of Streptococcus mutans and S. sobrinus. They also investigated xylitol's mechanism of action. METHODS: The authors compared cariogenic bacteria levels before and after exposure to xylitol products in children and adults. In the first study, 187 children received xylitol-containing snacks in school for four weeks. In the second study, two adults received xylitol candy for four weeks. Unstimulated saliva samples were taken from all subjects. Gingival samples also were taken from the adults. The authors plated the samples on selective microbiological media. Individual isolates were plated on media with varying concentrations of xylitol, and were identified using specific DNA probes. Genetic relatedness was determined via pulse-field gel electrophoresis. RESULTS: The children's salivary S. mutans levels remained stable before and after xylitol exposure. Further analysis of the S. mutans isolates was conducted for seven children. Bacteria from five of these children grew with 10 percent or less xylitol at baseline, while the bacteria from all seven children grew with 15 percent xylitol after exposure to the xylitol-containing snacks, suggesting that the S. mutans increased in tolerance to xylitol during exposure. Six children had isolates with the same genotype at both time points. S. mutans and S. sobrinus levels were reduced in one of the adults as a result of xylitol exposure, and the bacterial isolates became more xylitol tolerant. In the second adult, S. mutans and S. sobrinus levels increased, while the subject maintained the same proportion of susceptible and tolerant strains as that at baseline. CONCLUSIONS: Overall, consumption of xylitol-containing snacks and candy did not reduce S. mutans levels. However, bacteria from five children and one adult became more xylitol tolerant. CLINICAL IMPLICATIONS: These results provide a basis on which xylitol-containing products can be recommended and xylitol's mechanism of action can be explained to patients.

PMID: 11991460