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Category: microbes

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It turns out that we also have microbes called archaea living in and on our bodies. They are part of our microbiome (community of microbes living in and on us, which also includes bacteria, viruses, and fungi). Archaea constitute a domain or kingdom of single-celled microorganisms. These microbes are prokaryotes, meaning that they have no cell nucleus or any other membrane-bound organelles in their cells. Archaeal cells have unique properties that separate them from bacteria and eukaryotes. Archaea were initially classified as bacteria and thought to only exist in extreme environments (such as hot springs and salt lakes), and given the name archaebacteria, but this classification is now outdated. We now know that archaea live in less extreme places, including oceans, marshlands, animals, and humans.

So little is known about archaea that not even medical schools discuss this topic. This may be due to the fact that we currently don't know of any archaea that are human pathogens (that is, that cause illness) or parasitic. They are generally viewed as mutuals (the relationship is beneficial to both organisms) or commensals (they benefit, but don't help or harm the other organism). Humans appear to have low levels of archaea, and so far they have  been found in the human gut (part of digestion and metabolism), on the skin, and in subgingival dental plaque (and perhaps involved with periodontal disease). But studies rarely look for them. We don't know the importance or roles that they play in our bodies (but there are suspicions), but it turns out that drugs such as statins and the antibiotic metronidazole  are eliminating them.

Note that methanogens are archaea that excrete or produce methane as a metabolic byproduct in anoxic (no oxygen) conditions such as the gut. They help digest our food. The species Methanobrevibacter smithii  has been shown to be present in up to 95.7% of humans studied, and found to be the most abundant methanogen in the human gut, comprising up to as much as 10% of all anaerobes found in a healthy individual's colon. Anaerobes are organisms that require oxygen-free conditions to live. Some of the June 2015 article (by M. N. Lurie-Weinberger and U. Goph) excerpts from PLOS:

Archaea in and on the Human Body: Health Implications and Future Directions

Although they are abundant and even dominant members of animal microbiomes (microbiotas), from sponges and termites to mice and cattle, archaea in our own microbiomes have received much less attention than their bacterial counterparts. The fact that human-associated archaea have been relatively little-studied may be at least partially attributed to the lack of any established archaeal human pathogens. Clinically oriented microbiology courses often do not mention archaea at all, and most medical school and biology students are only aware of archaea as exotic extremophiles that have strange and eukaryotic-like molecular machinery. Since archaea have been known to be associated with the human gut for several decades, one would think that human microbiome studies may unravel new facets of archaea–human interactions...  ...continue reading "We Have Archaea In and On Our Bodies"

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This new research suggests possible future treatments in treating urinary tract infections (UTIs) by manipulating the person's diet and so influencing gut microbes and urinary pH (how acidic is the urine). These possible future treatments are different than what others are looking for, which are bacteria (probiotics) that one can take to prevent or treat UTIs. (Earlier posts on treating UTIs are here and here,)

The researchers found that during UTIs, humans secrete siderocalin which helps the body fight infection by depriving bacteria of iron (a mineral necessary for bacterial growth), and that samples that were less acidic, and closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.

The researchers found that the presence of small metabolites called aromatics, which vary depending on a person's diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer. Stay tuned for follow-up research. 

One of the researchers, Dr. Jeffrey P. Henderson, pointed out that physicians already know how to raise urinary pH with things like calcium supplements, and alkalizing agents are already used in the U.K. as over-the-counter UTI treatments. But knowing how to encourage the metabolites is trickier, but will involve dietary changes. Some good food sources include those rich in antioxidants: coffee, tea, colorful berries, cranberries, and red wine.

From Science Daily: A person's diet, acidity of urine may affect susceptibility to UTIs

The acidity of urine -- as well as the presence of small molecules related to diet -- may influence how well bacteria can grow in the urinary tract, a new study shows. The research may have implications for treating urinary tract infections, which are among the most common bacterial infections worldwide. Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.

"Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections," said senior author Jeffrey P. Henderson​, MD, PhD,...With this in mind, Henderson and his team, including first author Robin R. Shields-Cutler, a graduate student in Henderson's lab, were interested in studying how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth. "We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth," Henderson said. "Then we asked, what is special about the urine samples that restricted growth?"

The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily. The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.

"Age and sex did not turn out to be major players," Shields-Cutler said. "Of all the factors we measured, the only one that was really different between the two groups was pH -- how acidic or basic the urine was."Henderson said that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.

Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated.

"Physicians are very good at manipulating urinary pH," said Henderson, who treats patients with UTIs. "If you take Tums, for example, it makes the urine less acidic. But pH is not the whole story here. Urine is a destination for much of the body's waste in the form of small molecules. It's an incredibly complex medium that is changed by diet, individual genetics and many other factors."

After analyzing thousands of compounds in the samples, the researchers determined that the presence of small metabolites called aromatics, which vary depending on a person's diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer.

Henderson and his colleagues suspect that at least some of these aromatics are good iron binders, helping deprive the bacteria of iron. And perhaps surprisingly, these molecules are not produced by human cells, but by a person's gut microbes as they process food in the diet."Our study suggests that the body's immune system harnesses dietary plant compounds to prevent bacterial growth," Henderson said. "We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes."

Indeed, their results implicate cranberries among other possible dietary interventions. Shield-Cutler noted that many studies already have investigated extracts or juices from cranberries as UTI treatments but the results of such investigations have not been consistent.

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Drawing of colon seen from front (the appendix is colored red). Credit: Wikipedia.

For more than 100 years, the standard treatment for appendicitis has been surgery. Now a large Finnish study provides the best evidence to date that most patients can be treated with antibiotics alone.

How did the usual treatment of doing an appendectomy (appendix removal) arise? In 1886 Dr. Reginald Fitz, while investigating pelvic infections (which resulted in many deaths in those days), decided that an inflamed appendix progresses from a mild inflammation, to gangrene, then perforation, which would result in pelvic abscess.

This reason for an appendectomy (that it would prevent serious infection) became established in medical thought and still guides appendicitis management today. But nowadays we have antibiotics! And the researchers noted that some cases resolved on their own without any treatment.

And instead of the prevailing view for many years that the appendix is a "vestigial organ with no purpose",  it turns out that the appendix has a great reason for existence. It seems to provide a safe haven for good bacteria when gastrointestinal illness flushes those bacteria from the rest of the intestines. This reservoir of gut microbes then repopulates the digestive system following the illness.

It makes me wonder why some people get appendicitis and others don't - do they have inflammation for some reason so that their bacterial communities are out of whack (dysbiosis)? Would dietary changes help prevent recurrences?

From the NY Times: Antibiotics Are Effective in Appendicitis, Study Says

For more than 100 years, the standard treatment for appendicitis has been surgery. Now a large Finnish study provides the best evidence to date that most patients can be treated with antibiotics alone. The study, published Tuesday in JAMA, involved 530 patients aged 18 to 60 who agreed to have their treatment — antibiotics or surgery — decided at random. Three out of four who took antibiotics recovered easily, the researchers found. And none who had surgery after taking antibiotics were worse off for having waited.

The new study comes amid growing questions about the routine use of surgery to treat appendicitis, which strikes about 300,000 Americans a year, afflicting one out of 10 adults at some point in their lives.

The results only apply to uncomplicated appendicitis, stressed Dr. Paulina Salminen, a surgeon at Turku University Hospital in Finland and lead author of the new study. She and her colleagues excluded from their trial the 20 percent of patients with complicated cases — people with perforated appendices or abdominal abscesses, and those with a little, rock like blockage of the appendix called an appendicolith.

In the 1950s, soon after antibiotics were discovered, some doctors reported success using them to treat patients with appendicitis. But, Dr. Livingston wrote in his editorial, “So powerful is the perceived benefit of appendectomy for appendicitis that surgical treatment for appendicitis remains unquestioned, with seemingly little interest in studying the problem.”

Dr. Livingston also found that most appendices that perforate have already done so by the time the patient shows up at an emergency room. Those that have not perforated when the patient seeks medical help almost never do so. People with so-called uncomplicated appendicitis, he concluded, seem to have a different disease — one that can be treated with antibiotics.

“The reason we take the appendix out and do it as an emergency is the belief, dating back to 1886, that the appendix will eventually become gangrenous and cause a pelvic abscess,” Dr. Livingston said.

Even with the results of the Finnish study, many questions remain. A person who has had one episode of appendicitis is at higher than usual risk for another....Accumulating data has led other experts to raise an even more controversial idea: Perhaps antibiotics aren’t always necessary, either. It is possible, some researchers say, that most people with appendicitis would get better on their own if doctors did nothing. The Finnish team is now planning a clinical trial to test that theory.

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This month more research from researcher JJ Goedert about gut microbes in postmenopausal women and breast cancer. Very suggestive research was published September 2014 about the possibility of increasing a person's gut bacteria diversity to lower breast cancer risk. And even earlier research found that the human breast has a microbiome (community of microbes) that is different in healthy breasts as compared to cancerous breasts.

Now JJGoedert and others investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients (before treatment) as compared to 48 control patients (women without breast cancer). The average age of both groups was 62 years.The researchers analyzed the estrogens in the women's urine and the bacterial diversity in fecal samples using modern genetic analysis (such as 16S rRNA sequencing). They found in this study that postmenopausal women with breast cancer had lower gut bacteria diversity and somewhat different composition of gut bacteria as compared to women without breast cancer. They also said that what this means is unknown, that is,"whether these affect breast cancer risk and prognosis is unknown." Some differences in gut bacteria composition: women with breast cancer had lower levels of Clostridiaceae, Faecalibacterium, and Ruminococcaceae; and they had higher levels of Dorea and Lachnospiraceae.

Excerpt is from the Journal of the National Cancer Institute:

Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study.

We investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients, pretreatment, vs 48 control patients. Microbiota profiles in fecal DNA were determined by Illumina sequencing and taxonomy of 16S rRNA genes. Estrogens were quantified in urine....  Compared with control patients, case patients had statistically significantly altered microbiota composition  and lower α-diversity. Adjusted for estrogens and other covariates, odds ratio of cancer was 0.50 per α-diversity tertile. Differences in specific taxa were not statistically significant when adjusted for multiple comparisons. This pilot study shows that postmenopausal women with breast cancer have altered composition and estrogen-independent low diversity of their gut microbiota. Whether these affect breast cancer risk and prognosis is unknown.

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The good news is that not every tick is infected, but the bad news is that the CDC says that there are 14 known tick-borne diseases in the United States, and possibly 15 (if newly discovered Bourbon virus is included). Lyme disease is the most common, but people can be infected with more than one tick-borne illness simultaneously.  Three new diseases to watch for: Borrelia miyamotoi (bacteria carried by deer ticks), Heartland virus (carried by Lone Star Tick), and Bourbon virus. From Medical Xpress;

Beyond Lyme, new illnesses, more reason to watch for ticks

Lyme disease makes the headlines but there are plenty of additional reasons to avoid tick bites. New research highlights the latest in a growing list of tick-borne threats—a distant relative of Lyme that's easy to confuse with other illnesses.Monday's study suggests a kind of bacteria with an unwieldy name—Borrelia miyamotoi—should be on the radar when people in Lyme-endemic areas get otherwise unexplained summertime fevers. It's one of several recently discovered diseases linked to ticks in different parts of the country, a reminder to get tick-savvy no matter where you live.

The first U.S. case was reported in 2013 in New Jersey, an 80-year-old cancer survivor who over four months became increasingly confused, had difficulty walking and lost 30 pounds. Doctors found spiral-shaped bacteria in her spinal fluid that looked like Lyme but caused a relapsing fever more closely related to some other tick-borne illnesses. While treatable by antibiotics—the woman recovered—doctors know little about B. miyamotoi.

Researchers with Imugen Inc., a Massachusetts testing lab, tested blood samples from patients in Massachusetts, Rhode Island, New Jersey and New York whose doctors suspected tick-borne illnesses and used that lab. During the 2013 and 2014 tick seasons the lab found 97 cases of the new infection. That's roughly 1 percent of samples tested and close to the lab's detection of a better-known tick disease named anaplasmosis. ...Researchers then analyzed medical records from 51 of those patients, and found symptoms typically include a high fever, severe headache, chills and blood abnormalities—decreases in infection-fighting and blood-clotting cells. 

The bacterium is carried by deer ticks, also known as blacklegged ticks, which also can spread Lyme and two other illnesses, babesiosis and anaplasmosis.

 Two new tick-borne viruses were recently discovered in the Midwest, and neither has a specific treatment.The Centers for Disease Control and Prevention has confirmed nine cases of Heartland virus, and one death, with other reports under investigation, said CDC entomologist Roger Nasci. Symptoms include fever, fatigue, headaches, muscle aches, diarrhea and low blood counts. Identified in Missouri, the virus also was reported in Tennessee and Oklahoma, although the Lone Star tick that spreads it lives around the East and Southeast.

Then there's the Bourbon virus, with similar symptoms, discovered last year after the death of a Kansas man and named for his home county. Another patient, in Oklahoma, recovered. The Kansas man had found an embedded tick days before getting sick, and CDC researchers are searching for the culprit species.

The CDC counts 14 illnesses linked to specific U.S. tick species, not including the Bourbon virus still being studied. Lyme is the most common, with about 30,000 cases reported each year, although CDC has estimated that the true number could be 10 times higher. It's too early to know how widespread the newly discovered illnesses are. But people can be infected with more than one tick-borne illness simultaneously, complicating care.

Deer tick            Lone Star Tick   Credit:Wikipedia

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New research shows that wearing contact lenses could significantly change the bacteria of the eye’s surface, making it more susceptible to infection. NYU Langone Medical Center researchers analyzed swabs from both contact-wearers and non-wearers to determine the number and type of bacterial species that lived on the surface of their eyes—the eye’s microbiome as well as the skin below the eye.

They found that the eye microbiome of contact lens wearers is more similar in composition to the microbiome of their skin than the eye microbiome of non-lens wearers.

Note that infections often come when people don’t take proper care of their lenses—sleeping in them overnight, or not cleaning them well or often enough so most eye doctors have shifted to recommending daily lenses. 

From Medical News Today: Alterations to the eye microbiome of contact lens wearers may increase infections

Contact lens wearers - ever wondered why you are more likely to experience eye infections than your contacts-less friends? Researchers from NYU Langone Medical Center in New York City think they may have found the answer, in a study that used high-precision genetic tests to map the human microbiome....the NYU Langone researchers report that micro-organisms residing in the eyes of people who wear contact lenses daily more closely resemble micro-organisms residing in eyelid skin than the bacteria usually found in the eyes of people who do not wear contacts.

The researchers took hundreds of swabs of different parts of the eye, including the skin directly beneath the eye. Genetic analysis of swabs and used contact lenses allowed the team to identify which bacteria were present. Comparing nine contact lens wearers with 11 non-contacts users, the team found three times the usual proportion of the bacteria Methylobacterium, Lactobacillus, Acinetobacter and Pseudomonas on the eye surfaces (conjunctiva) of contact lens wearers than on the eye surfaces of the control group.

Examining the bacterial diversity using a plotted graph, the team observed that the eye microbiome of contact lens wearers is more similar in composition to the microbiome of their skin than the eye microbiome of non-lens wearers. 

Interestingly, the researchers say, Staphylococcus bacteria was found in greater amounts in the eyes of non-lens wearers. Staphylococcus is linked with eye infections, but is usually more prominent on the skin. However, the researchers are unable to explain why non-lens wearers have greater amounts of this bacteria, despite this group traditionally having fewer eye infections than people who wear contacts.

Study author Dr. Jack Dodick, professor and chair of ophthalmology at NYU Langone, says:"There has been an increase in the prevalence of corneal ulcers following the introduction of soft contact lenses in the 1970s. A common pathogen implicated has been Pseudomonas. This study suggests that because the offending organisms seem to emanate from the skin, greater attention should be directed to eyelid and hand hygiene to decrease the incidence of this serious occurrence."

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I know of a number of people in NY and NJ who have been struggling for years with persistent Lyme disease. So this research with the possibility of treatments that actually work is fantastic. And it gives support to all those people who say they still have Lyme disease after antibiotic treatment, but the medical establishment says they're wrong -  that it's all their mind or due to something else. Yes, they still have Lyme disease from persister cells that avoided the antibiotic treatment! Persister cells are drug-tolerant,dormant variants of Borrelia burgdorferi  (the bacterium that causes Lyme disease). And perhaps pulse-dosing antibiotics may work to get rid of the persister cells. The antibiotic they successfully used in the research is ceftriaxone (a cephalosporin antibiotic) - but only in cultures grown in a lab. Further research is needed. From Science Daily:

Researchers' discovery may explain difficulty in treating Lyme disease

North­eastern Uni­ver­sity researchers have found that the bac­terium that causes Lyme dis­ease forms dor­mant per­sister cells, which are known to evade antibi­otics. This sig­nif­i­cant finding, they said, could help explain why it's so dif­fi­cult to treat the infec­tion in some patients.

In other chronic infec­tions, Lewis' lab has tracked the resis­tance to antibi­otic therapy to the pres­ence of per­sister cells--which are drug-tolerant, dor­mant vari­ants of reg­ular cells. These per­sister cells are exactly what they've iden­ti­fied here in Bor­relia burgdor­feri, the bac­terium that causes Lyme disease.The researchers have also reported two approaches--one of them quite promising--to erad­i­cate Lyme dis­ease, as well as poten­tially other nasty infections.

Lyme dis­ease affects 300,000 people annu­ally in the U.S., according to the Cen­ters for Dis­ease Con­trol and Pre­ven­tion, and is trans­mitted to people via bites from infected black­legged ticks. If caught early, patients treated with antibi­otics usu­ally recover quickly. How­ever, about 10 to 20 per­cent of patients, par­tic­u­larly those diag­nosed later, who have received antibi­otic treat­ment may have per­sis­tent and recur­ring symp­toms including arthritis, muscle pain, fatigue, and neu­ro­log­ical prob­lems. These patients are diag­nosed with Post-treatment Lyme Dis­ease Syndrome.

In addi­tion to iden­ti­fying the pres­ence of these per­sister cells, Lewis' team also pre­sented two methods for wiping out the infection--both of which were suc­cessful in lab tests. One involved an anti-cancer agent called Mit­o­mycin C, which com­pletely erad­i­cated all cul­tures of the bac­terium in one fell swoop. How­ever, Lewis stressed that, given Mit­o­mycin C's tox­i­city, it isn't a rec­om­mended option for treating Lyme dis­ease, though his team's find­ings are useful to helping to better under­stand the disease.

The second approach, which Lewis noted is much more prac­tical, involved pulse-dosing an antibi­otic to elim­i­nate per­sis­ters. The researchers intro­duced the antibi­otic a first time, which killed the growing cells but not the dor­mant per­sis­ters. But once the antibi­otic washed away, the per­sis­ters woke up, and before they had time to restore their pop­u­la­tion the researchers hit them with the antibi­otic again. Four rounds of antibi­otic treat­ments com­pletely erad­i­cated the per­sis­ters in a test tube.

"This is the first time, we think, that pulse-dosing has been pub­lished as a method for erad­i­cating the pop­u­la­tion of a pathogen with antibi­otics that don't kill dor­mant cells," Lewis said. "The trick to doing this is to allow the dor­mant cells to wake up.

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Interesting, but very preliminary observational research, and there could be various explanations for the results suggesting that the microbiome (community of microbes) of a toddler's gut may influence their behavior. The researchers did not think these differences were diet related, but they had not studied the diet in depth. From Science Daily:

Toddler temperament could be influenced by different types of gut bacteria

The microbiome of a toddler's gut may influence their behavior, a new study suggests. Researchers from The Ohio State University studied microbes from the gastrointestinal tracts of children between the age of 18 and 27 months, and found that the abundance and diversity of certain bacterial species appear to impact behavior, particularly among boys. The correlation exists even after the scientists factored in history of breastfeeding, diet and the method of childbirth -- all of which are known to influence the type of microbes that populate a child's gut. 

Christian and study co-author, microbiologist Michael Bailey, PhD, studied stool samples from 77 girls and boys, and found that children with the most genetically diverse types of gut bacteria more frequently exhibited behaviors related with positive mood, curiosity, sociability and impulsivity. In boys only, researchers reported that extroverted personality traits were associated with the abundances of microbes from the Rikenellaceae and Ruminococcaceaefamilies and Dialister and Parabacteroides genera.

"There is definitely communication between bacteria in the gut and the brain, but we don't know which one starts the conversation," said Dr. Bailey...Overall, associations of temperament with the gut microbiome in girls were fewer and less consistent than boys. However, in girls, behaviors like self-restraint, cuddliness and focused attention were associated with a lower diversity of gut bacteria, while girls with an abundance of Rikenellaceae appeared to experience more fear than girls with a more balanced diversity of microbes.

To identify correlations between gut bacteria and temperament, researchers asked mothers to assess kid's behavior using a questionnaire which measures 18 different traits that feed into three composite scales of emotional reactivity: Negative Affect, Surgency/Extraversion and Effortful Control. Scientists looked at the different genetic types and relative quantity of bacteria found in the toddler's stool samples along with their diets.

Similar to other child behavior studies, researchers separated their findings by gender to analyze temperament. Overall, the study found few differences in the abundance and types of gut microbiota between girls and boys.Both researchers say that parents shouldn't try to change their child's gut microbiome just yet. Scientists still don't know what a healthy combination looks like, or what might influence its development.

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Image result for pills wikipedia My last post was about a recent Medscape article discussing whether probiotics can be used to treat urinary tract infections (UTIs) (answer: probiotics are promising, but too little is known right now to recommend any). Two alternative treatments that the article did not discuss were drinking cranberry juice or taking cranberry supplements (studies are currently mixed regarding their effectiveness in UTIs - possibly due to varying cranberry products and doses used) and taking D-mannose supplements (whether as a powder or pill).

D-mannose is recommended on alternative medical sites as an effective treatment for UTIs caused by E.coli, including recurrent UTIs. Studies show that up to 90% of UTIs are caused by E. coli.The majority of both males and females writing comments about UTI treatments on these sites and for D-mannose product reviews (on Amazon) rave about D-mannose as the only treatment that worked for them after suffering from recurrent UTIs (antibiotics typically did not work well for them).

D-mannose is a naturally occurring sugar found in a number of fruits, especially cranberries and blueberries. D-mannose is effective because it attaches to E. coli bacteria, and prevents them from attaching to the walls of the urinary tract. (Researchers write that D-mannose "inhibits bacterial adhesion to uroepithelial cells.") Persons taking D-mannose are also advised to drink plenty of water, which then flushes out the bacteria.

The typical dose of D-mannose for UTI treatment is 500 mg, in capsule or powder form, taken in a glass of water or juice, every few hours for five days (perhaps 5 or 6 tablets a day). Then continue taking for a few days after all symptoms go away to make sure all the bacteria are flushed out of the urinary tract.

Many long-term recurrent UTI sufferers continue taking D-mannose at lower doses to prevent the UTIs from recurring. There are no known side-effects. D-mannose is easily found at grocery stores, health food stores, and online.

After doing a D-mannose and urinary tract infection search using PubMed (from Medline, the National Institute of Health), I found that currently there is only one published study looking at the use of D-Mannose in urinary tract infections.

The 2014 study by B. Kranjcec, D. Papes, and S. Altarac looked at the effectiveness of D-mannose powder for recurring urinary tract infections in women. 308 women with a history of recurrent UTIs were first treated with an antibiotic (ciprofloxacin) for an UTI, and then were randomly assigned to one of 3 groups for 6 months. The 3 groups were: D-mannose (2 g of D-mannose in 200 ml water daily), or prophylactic antibiotics (50 mg Nitrofurantoin daily) or a control group that didn't take anything (no prophylaxis).

Results were that 98 patients (31.8%) had a recurrent UTI. Of those 98, 14.6% (15 women) were in the D-mannose group, 20.4% (21 women) in the Nitrofurantoin antibiotic group, and 60.8%  (62 women) in the no treatment (no prophylaxis) group. In other words, the D-mannose group did the best in preventing recurrences, even better than the antibiotic. 

From World Journal of Urology: D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial.

Overall 98 patients (31.8%) had recurrent UTI: 15 (14.6) in the D-mannose group, 21 (20.4) in Nitrofurantoin group, and 62 (60.8) in no prophylaxis group, with the rate significantly higher in no prophylaxis group compared to active groups (P < 0.001). Patients in D-mannose group and Nitrofurantoin group had a significantly lower risk of recurrent UTI episode during prophylactic therapy compared to patients in no prophylaxis group (RR 0.239 and 0.335, P < 0.0001). In active groups, 17.9% of patients reported side effects but they were mild and did not require stopping the prophylaxis. Patients in D-mannose group had a significantly lower risk of side effects compared to patients in Nitrofurantoin group (RR 0.276, P < 0.0001), but the clinical importance of this finding is low because Nitrofurantoin was well tolerated.

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Amusing but also scary. The negative effects on the gut microbes of one person consuming an all fast food diet for 10 days occurred very quickly, and his gut microbes did not recover even 2 weeks after the fast food diet ended. Biggest problem seemed to be loss of gut diversity - about 40% of his gut bacterial species. Loss of gut diversity is considered a sign of ill health. Written by Tim Spector, with Tom Spector's assistance, from The Conversation:

Your gut bacteria don’t like junk food – even if you do

When Morgan Spurlock famously spent a month eating large portions of McDonalds for the purposes of his documentary Supersize Me, he gained weight, damaged his liver and claimed to have suffered addictive withdrawal symptoms. This was popularly attributed to the toxic mix of carbs and fat plus the added chemicals and preservatives in junk foods. But could there be another explanation?

We may have forgotten others who really don’t enjoy fast food. These are the poor creatures that live in the dark in our guts. These are the hundred trillion microbes that outnumber our total human cells ten to one and digest our food, provide many vitamins and nutrients and keep us healthy. 

For the sake of science and research for my book The Diet Myth, I have been experimenting with several unusual diets and recorded their effects on my gut microbes...My son Tom, a final year student of genetics at the University of Aberystwyth suggested an additional crucial experiment: to track the microbes as they changed from an average western diet to an intensive fast food diet for over a week.

I wasn’t the ideal subject since I was no longer on an average diet, but Tom, who like most students enjoyed his fast food, was. So he agreed to be the guinea pig on the basis that I paid for all his meals and he could analyse and write up his results for his dissertation. The plan was to eat all his meals at the local McDonalds for ten days. He was able to eat either a Big Mac or Chicken nuggets, plus fries and Coke. For extra vitamins he was allowed beer and crisps in the evening. He would collect poo samples before, during and after his diet and send them to three different labs to check consistency.

While it was clear the intensive diet had made him feel temporarily unwell, we had to wait a few months for the results to arrive back....They all told the same story: Tom’s community of gut microbes (called a microbiome) had been devastated.

Tom’s gut had seen massive shifts in his common microbe groups for reasons that are still unclear. Firmicutes were replaced with Bacteroidetes as the dominant type, while friendly bifidobacteria that suppress inflammation halved. However the clearest marker of an unhealthy gut is losing species diversity and after just a few days Tom had lost an estimated 1,400 species – nearly 40% of his total. The changes persisted and even two weeks after the diet his microbes had not recovered. Loss of diversity is a universal signal of ill health in the guts of obese and diabetic people and triggers a range of immunity problems in lab mice.

That junk food is bad for you is not news, but knowing that they decimate our gut microbes to such an extent and so quickly is worrying...We rely on our bacteria to produce much of our essential nutrients and vitamins while they rely on us eating plants and fruits to provide them with energy and to produce healthy chemicals which keep our immune system working normally.

We are unlikely to stop people eating fast food, but the devastating effects on our microbes and our long term health could possibly be mitigated if we also eat foods which our microbes love like probiotics (yogurts), root vegetables, nuts, olives and high-fibre foods. What they seem to crave, above all else, is food diversity and a slice of gherkin in the burger just isn’t enough.

Tom Spector. Credit: Tim Spector