Information

Is diarrhoea advantageous to the microbe?


Diarrhoea is a common side effect of many feco-orally transmitted bacterial infections. How does diarrhoea help the pathogen? Should it not have a selective evolutionary advantage? Do all symptoms of the disease need to have a selective advantage for the pathogen? All I can think of is that a more liquidy stool would lead to further ease in feco-oral transmission. Is this true?


Vibrio cholera for example is actively causing diarrhoea, by stimulating the CFTR channel to excrete chlorine ions, which will attract water from the gut tissue.

The answer of the function seems obvious: to promote dispersal in the environment and as such infect/find new hosts. See also: extended phenotype (Richard Dawkins): how genes in one organism (mostly a parasite) influence the behaviour of another organism (mostly the host of the parasite) to increase the (reproductive) success of the gene/parasite. Also: numerous (some horrifying) examples in Parasite Rex (by Carl Zimmer)


How diarrhea pathogens switch into attack mode at body temperature

Many bacterial pathogens excrete toxins as soon as they have entered the host in order to suppress its immune response. Researchers at Ruhr-Universität Bochum (RUB) have analysed what happens on the molecular level when the diarrhea pathogen Yersinia pseudotuberculosis switches into attack mode. To this end, they examined so-called RNA thermometers, which signal to the bacteria whether they are in the host.

In collaboration with colleagues from the Helmholtz Institute for Infection Research in Braunschweig, they also showed that bacteria with deactivated RNA thermometers can no longer trigger an infection. The journal PLOS Pathogens reports about the study online on January 17, 2020.

RNA thermometer melts at 37 degrees Celcius

"We knew from previous studies that Yersinia bacteria are very sensitive to temperature changes and recognise that they are in their host on the basis of body temperature," says Professor Franz Narberhaus from the RUB Chair of Microbial Biology. RNA thermometers are responsible for temperature measurement. They are sections in the messenger RNA of many genes that contain the blueprint for disease-causing proteins.

At low temperatures, i.e. outside the host, RNA thermometers prevent the RNA from being read and translated into proteins. Only after successful infection of the warm-blooded host, i.e. at a temperature of around 37 degrees Celsius, do the RNA structures melt. They can then be written into proteins that have a harmful effect on the host. In the current publication, the scientists describe the underlying melting mechanism of the RNA thermometer for one of the toxins of Yersinia pseudotuberculosis, namely the CnfY-Toxin.

Bacteria with non-functional thermometers do not cause illness

PhD student Christian Twittenhoff from Bochum used isolated cell components of the diarrhea pathogen to show which structure the RNA thermometer for the CnfY toxin assumes and where it melts. The biologist created a model that documents how the thermometer opens. It also shows how the ribosome -- the cell component on which the messenger RNA is translated into a protein -- docks to the messenger RNA.

In cooperation with the group headed by Professor Petra Dersch, formerly at Helmholtz Institute in Braunschweig, currently at the University of Münster, the researchers moreover demonstrated the role of the RNA thermometer in the disease process. They infected mice with Yersinia bacteria that either had functioning RNA thermometers or inactivated RNA thermometers that could not melt at 37 degrees Celsius. The bacterial strains with modified RNA thermometers were not able to make mice ill. "The results have shown how important very short regulatory RNA sequences can be for the successful course of infection of a bacterium," concludes Christian Twittenhoff, lead author of the study.

Similar mechanisms suspected in other bacteria

Christian Twittenhoff compared the gene of the CnfY toxin with toxin genes of other pathogens using bioinformatic methods. The analysis suggests that other toxin genes might also be regulated by RNA thermometers. "Even though the sequences are very different, we are able to predict which RNA structures are likely to act as thermometers," he explains.

"RNA thermometers function via a very simple mechanism, which has probably proved its efficacy in the course of evolution and has therefore developed many times and independently of each other," assumes Franz Narberhaus. In principle, it is possible to prevent bacterial infection by preventing the melting of such RNA structures. "However, we don't yet know any substances that freeze RNA thermometers in the closed state," continues Narberhaus.


Types of diarrhea and causes

A bout of diarrhea that lasts no more than two weeks is referred to as acute diarrhea and is most often caused by a viral infection, according to the ACG. The most common diarrhea-causing virus for adults is norovirus, which is often referred to as "cruise ship diarrhea" due to its unfortunate tendency to infect sea-faring vacationers. Rotavirus, another diarrhea-inducing virus, is very common in young children.

Other causes of acute diarrhea include bacterial infection, which is often referred to as "traveler's diarrhea," or, in some parts of the world, "Montezuma's revenge." But those who come down with this uncomfortable ailment aren't the victims of an ancient curse they're usually the victims of the bacteria enterotoxigenic Escherichia coli (ETEC), according to Dr. Ian Lustbader, a clinical associate professor of medicine and a gastroenterologist at New York University's Langone Medical Center.

A final common cause of acute diarrhea is parasites, which can be ingested when a person consumes contaminated food or water, Lustbader told Live Science.

Diarrhea that lasts longer than four weeks is known as chronic diarrhea. Like acute diarrhea, chronic diarrhea has many causes. According to Lustbader, these causes include:

  • Infectious causes (most commonly parasites)
  • Osmotic and malabsorption causes (which result in too much water being absorbed into the bowel), such as Celiac disease and lactose intolerance
  • Inflammatory causes, such as ulcerative colitis or Crohn's disease
  • Intestinal ischemia, or lessened blood flow to the intestine
  • Certain cancer therapies, like radiation
  • Certain medications, such as antibiotics

Diarrhea and deaths from it are more prevalent in third-world countries. This is due to lack of clean drinking water and poor sanitation conditions. Many organizations like PATH and WHO, are working to solve problems that lead to diarrhea deaths in children by providing:

  • Immunizations for certain causes
  • Filters for drinking water
  • Education for families
  • Better diagnosis and treatment plans

Chaining up diarrhoea pathogens

Two clumped clones (red and green) of salmonella are held together by IgA antibodies. Credit: Emma Slack / ScopeM, ETH Zurich

Researchers have clarified how vaccinations can combat bacterial intestinal diseases: vaccine-induced antibodies in the intestine chain up pathogens as they grow in the intestine, which prevents disease and surprisingly also hinders the spread of antibiotic resistance.

Vaccinations are known to protect against pathogens such as bacteria or viruses. They direct the body to form protective antibodies (IgA), and have been successfully used against some intestinal infections.

However, exactly how intestinal antibodies – known as secretory IgA – protect against infections was previously unclear. A group of researchers led by ETH Senior Assistant Emma Slack, have now used the example of salmonella-based diarrhoea to show that secretory IgA works very differently to how we previously assumed.

In a study published recently in the journal Nature, the researchers showed that vaccine-induced IgA effectively "enchained" the pathogens in the intestine: IgA binds the bacteria's daughter cells to each other during cell division. Although the enchained bacteria can continue to multiply, all their offspring remain trapped in these clumps. This clumping of genetically homogeneous bacteria prevents the attack of the intestinal tissue, accelerates the excretion of the pathogen and prevents genetic exchange between bacteria enchained in different clumps.

Agglutination only in the test tube

That antibodies and bacteria clump, a process known as agglutination, has long been known. However, this only occurs when antibodies and bacteria are present in high densities and so often come into contact with each other. "In the test tube, it happens in textbook fashion. There are high enough concentrations of antibodies and bacteria, so they often collide," says Dr. Slack.

In the intestine, however, such high pathogen densities are the exception: "this makes it much less likely that the IgA-coated bacteria will collide," explains Dr. Slack. Despite this, research has long observed that such clumps do form in the intestine – meaning there must have been another explanation for the clumping.

Antibody enchain Salmonella (green). This prevents the transfer of DNA (yellow rings) to other cells. The violet cells are swimming freely. Credit: Thierry Sollberger

Bacterial growth controls clumping

Dr. Slack and her group have now demonstrated for the first time that clumps form even with a low pathogen density, and that this does not depend on the concentration of the bacteria. The driving force behind the formation of the clumps is the pathogens' growth rate. The IgA antibodies attach themselves so strongly to bacteria that they do not release them even when the pathogens divide. Thus both daughter cells remain stuck together. In this way, the IgA antibodies enchain all the offspring of a single, rapidly dividing bacterium.

Clumps hinder disease

"The clever thing about clump formation is that the antibodies don't kill the bacteria, which in the worst case could lead to a violent immune response. They simply prevent the microbes from interacting with the host, among themselves or with close relatives," says Wolf-Dietrich Hardt, Professor of Microbiology at ETH Zurich, who played a key role in the study.

Fighting intestinal infections using vaccination thus has several advantages: antibody-bacteria clumps cannot approach the intestinal wall, which prevents the intestinal mucosa from becoming inflamed. The intestine also gets rid of the clumps quickly, and after a few days they are cleared in the faeces. "The system is efficient. It is easier to get rid of a whole clump than to capture and eliminate many individual bacterial cells," says Dr. Slack.

No exchange of resistance genes

Intestinal vaccination could help to overcome the antibiotic resistance crisis. Vaccination decreases the incidence of diseases potentially requiring antibiotic usage, which would automatically reduce the development and spread of resistance to antibiotics. IgA-driven clump formation also directly prevents genetic exchange between individual captured bacterial populations. Bacteria often exchange genes in the form of plasmids (ring-shaped DNA molecules), which frequently carry the feared antibiotic resistance genes. To exchange plasmids, however, the bacterial cells have to touch, which they can't do if they are stuck in separate clumps.

Livestock vaccination

The researchers used oral vaccines made from killed salmonella and E. coli bacteria. They suggested that this strategy could also be used against the pathogens of other intestinal diseases such as Shigella or Listeria.

The largest area of application for salmonella vaccination could be in farm animals such as pigs, which often act as a reservoir for antibiotic-resistant pathogens. Humans can become infected by contact with these animals and their raw meat. A vaccination for humans could also be feasible, which would benefit people working in disaster or epidemic areas, or those travelling in regions where bowel infections are common.


How can I treat or prevent dehydration caused by diarrhea?

To treat or prevent dehydration, you need to replace lost fluids and electrolytes—called rehydration therapy—especially if you have acute diarrhea. Although drinking plenty of water is important in treating and preventing dehydration, you should also drink liquids that contain electrolytes, such as the following:

If you are an older adult or have a weak immune system, you should also drink oral rehydration solutions, such as Pedialyte, Naturalyte, Infalyte, or CeraLyte. Oral rehydration solutions are liquids that contain glucose and electrolytes. You can make oral rehydration solutions at home (PDF, 184KB) .


Antibiotics for Intestinal Bacterial Infection:

Traveller’s diarrhea:

Traveller’s diarrhea occurs during the first 2-3 week of a tour, when the travellers consume contaminated foods and drinks. Travellers diarrhea is a self-limiting infection. Less than 1% of patients get admitted into hospital.
Only rehydration is recommended for the patients with traveller’s diarrhea.
Although several antibiotics are used to treat several cases of travellers diarrhea. These antibiotics are:

Levofloxacin is effective for traveller’s diarrhea. Although azithromycin is more effective than it.

Several antibiotic is also prescribed for traveller’s diarrhea patients. But they show resistance in some cases. These are:

Salmonellosis:

Several non-typhoidal bacteria cause salmonellosis. They are Salmonella enterica and Salmonella bongori. The first one has several serotypes such as Salmonella enterica serotypes Enteritidis Salmonella enterica serotypes Typhimurium, Salmonella enterica serotypes Newport and Salmonella enterica serotypes Heidelberg.

Symptoms of salmonellosis include diarrhea, bloody stools, fever, and headache.

Antibiotics used for salmonellosis are:

  • Fluoroquinolones- ciprofloxacin
  • Ampicillin
  • Azithromycin
  • Third generation cephalosporins- cefotaxime

Normal patients should use these antibiotics for 7-10 days and immunocompromised people should take these antibiotics for 14 days.

Shigellosis:

Three serogroups of Shigella (Serogroup A-C: S. dysenteriae, S. flexneri, S. boydii)and one serotype (Serogroup D: S. sonnei) cause shigellosis.

Symptoms of Shigellosis include diarrhea, abdominal pain, and fever.

Antibiotics used for shigellosis are:

Campylobacteriosis:

Campylobacter jejuni cause Campylobacteriosis.

Symptoms of Campylobacteriosis include abdominal cramps, bloating and fever.

Antibiotics used for Campylobacteriosis are:

Yersiniosis:

Yersinia enterocolitica cause yersinosis.

Symptoms of Yersiniosis include fever, vomiting, stomach pain, and bloody diarrhea. Patients with this infection don’t need to take antimicrobial therapy. But in case of severe infection, patients must take the following antibiotics.

  • Ciprofloxacin
  • Doxycycline
  • Ampicillin
  • Combination of doxycycline and gentamicin.
  • Third generation cephalosporins- cefotaxime.

In most cases, patients get recovered from yersiniosis without any treatment.

Listeriosis:

Listeria monocytogenes commonly found on food causes listeriosis. This infection often causes a high mortality rate. So patients need effective treatment.

Symptoms of Listeriosis include fever, diarrhea and muscle aches.

Antibiotics used for Listeriosis are:

Other antibiotics which are of the second choice for this infection include:

  • Trimethoprim-sulfamethoxazole
  • Erythromycin
  • Vancomycin and
  • Fluoroquinolone.

Cephalosporin doesn’t work properly against Listeria.

Cholera:

Vibrio cholerae cause cholera. Consumption of foods and drinks contaminated by this bacteria cause cholera.

Symptoms of cholera include watery diarrhea, rice-water stools, vomiting, dry mouth, and rapid heart rate. Vibrio bacteria show resistance to co-trimoxazole, tetracycline, and doxycycline.

Antibiotics used for cholera are:

Several antibiotics such as co-trimoxazole, tetracycline, or doxycycline were also recommended. But due to growing antibiotic resistance, they are not used nowadays.

E. coli associated diarrhea:

The most discussed E. coli strain is E. coli O157: H7. Other strains that cause intestinal infections are Enterotoxic/enteropathogenic E. coli (ETEC, EPEC), Enteroinvasive/ enterohemorrhagic E. coli (EIEC, EHEC), Shiga toxin producing or verocytotoxin producing E. coli (STEC/VTEC)

Symptoms of E. coli infection include diarrhea, Watery diarrhea (in severe cases rice water stool) vomiting, fever, abdominal cramps, and malaise.

Antibiotics used for this infection are:

Clostridium difficle cause clostridial infection. This is a food poisoning bacterium.

Symptoms of clostridial infetion include watery diarrhea (three times a day or ten times for mild or acute infection respectively), abdominal pain, rapid heart rate, bloody stool, and fever.

Antibiotics used for shigellosis are:

Taking probiotics helps you maintain better gut health and prevent intestinal bacterial infection or gastroenteritis. Probiotics regulate the gut bacteria to keep in balance and thus improve gut health.


Antibiotic use for travelers' diarrhea favors particularly resistant super bacteria

Every year, millions of travellers visit countries with poor hygiene, and approximately one third of them return home carrying antibiotic-resistant ESBL intestinal bacteria. Most of them remain unaware of this, as the bacteria cause no symptoms. High-risk areas for contracting ESBL bacteria are South and South-East Asia, Africa and Latin America.

Diarrhoea is the most common health complaint for people who travel to poor regions of the world. Those contracting diarrhoea have an increased risk of ESBL acquisition, and if they choose to they treat it with antibiotics, the risk becomes multiplied. A Finnish study led by Professor Anu Kantele and published two years ago showed that among people travelling to high-risk areas, those contracting diarrhoea and taking antibiotics, up to 80% brought ESBL super bacteria home with them.

A follow-up study led by Professor Kantele has now established that antibiotics taken while abroad not only render the tourist susceptible to an ESBL infection, but also lead to the most resistant strains of these bacteria being selected.

"ESBL bacteria are resistant to penicillins and cephalosporins, which is why infections caused by them are treated with antibiotics from other groups, such as fluoroquinolones (e.g. ciprofloxacin). When we analysed the patients with ESBL more closely, we found that among those who had not resorted to using antibiotics, 37% had an ESBL strain resistant to fluoroquinolone. As for the travellers who had taken fluoroquinolone, 95% had a strain of ESBL resistant to fluoroquinolone and, indeed, a variety of other antibiotics. Antibiotic use thus implies selecting ESBL strains with the broadest spectrum of resistance," Kantele explains.

"The finding makes sense. When we take an antibiotic, the bacteria that survive in our digestive system are those resistant to the treatment."

Antibiotic resistance can be transferred between bacteria through a package containing a variety of resistance genes, meaning that one package may contain resistance to several types of antibiotics. Indeed, most fluoroquinolone-resistant ESBL strains were also found resistant to certain other types of antibiotics the resistance to which is known to be transferred in the same gene packages that transfer ciprofloxacin resistance.

"In practice this means that travellers pick up the most resistant strains of ESBL, and we are left with dwindling treatment options for ESBL infections," states Kantele.

Antibiotic resistance is a serious threat

An ESBL infection rarely manifests through symptoms. Still, even a symptomless carrier can pass on the bacteria and, with ill luck, it can cause a severe, even life-threatening disease. Kantele emphasises that antibiotic resistance is one of the biggest threats to health care. If antibiotics loose their efficacy, many infectious diseases now treated successfully with antibiotics may become lethal again.

"The spread of resistant strains of bacteria makes the situation worse. Therefore, unnecessary use of antibiotics should be avoided also while travelling. Diarrhoea mostly remains mild or moderate, and no antibiotics are needed in such cases for healthy adults. They should just make sure to keep hydrated. And, if necessary, anti-motility medication can be taken in small amounts to alleviate the symptoms."

The study recently published in Travel Medicine and Infectious Disease recruited Finnish travellers visiting the Travel Clinic at Aava Medical Centre as research subjects. The subjects gave a stool sample both before travel and immediately upon return, and answered questionnaire forms. A total of 90 people, all of whom had contracted an intestinal strain of ESBL bacteria while abroad, were selected to participate in the follow-up study. The susceptibility of the various strains to several different antibiotics was examined, and the results compared to such particulars as destination, age of traveller, travellers' diarrhoea, and antibiotic treatments used.

The study was carried out in cooperation between the University of Helsinki, the Helsinki University Hospital, the Karolinska Institutet and the Travel Clinic at Aava Medical Centre.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.


Bacterial and Fungal Microbiota Changes Distinguish C. difficile Infection from Other Forms of Diarrhea: Results of a Prospective Inpatient Study

This study sought to characterize the bacterial and fungal microbiota changes associated with Clostridium difficile infection (CDI) among inpatients with diarrhea, in order to further explain the pathogenesis of this infection as well as to potentially guide new CDI therapies. Twenty-four inpatients with diarrhea were enrolled, 12 of whom had CDI. Each patient underwent stool testing for CDI prior to being treated with difficile-directed antibiotics, when appropriate. Clinical data was obtained from the medical record, while each stool sample underwent 16S rRNA and ITS sequencing for bacterial and fungal elements. An analysis of microbial community structures distinct to the CDI population was also performed. The results demonstrated no difference between the CDI and non-CDI cohorts with respect to any previously reported CDI risk factors. Butyrogenic bacteria were enriched in both CDI and non-CDI patients. A previously unreported finding of increased numbers of Akkermansia muciniphila in CDI patients was observed, an organism which degrades mucin and which therefore may provide a selective advantage toward CDI. Fungal elements of the genus Penicillium were predominant in CDI these organisms produce antibacterial chemicals which may resist recovery of healthy microbiota. The most frequent CDI microbial community networks involved Peptostreptococcaceae and Enterococcus, with decreased population density of Bacteroides. These results suggest that the development of CDI is associated with microbiota changes which are consistently associated with CDI in human subjects. These gut taxa contribute to the intestinal dysbiosis associated with C. difficile infection.

Keywords: Clostridium difficile bacterial diarrhea fungal microbiome.


Endotoxins Vs Exotoxins

Micro-organisms such as bacteria, fungi produce toxic substances that boost up the infection and diseases through damaging the host tissues and by troubling the immune system. The most potent and known natural bacterial toxin is Botulinum neurotoxin which has essential uses in research and medical science. At present, toxins are used as tools in cellular biology and neurobiology to develop anticancer drugs and other medicines. Toxins from bacteria act as virulence factors that influence the functions of the host cell to help microbial infections. Toxins produced from bacteria can be either endotoxins or exotoxins. These toxins play a pivotal role in leading various diseases and infections.

Endotoxins

Endotoxins are lipopolysaccharides toxic substances which are part of the outer membrane of the gram-negative bacteria. Generally, it is released when the bacterium is killed, or cell lyses by the immune system due to action of phagocytic digestion or specific antibiotic actions. It is found in the body of the following bacteria species:


High-Fiber Fruits

The College of Agriculture & Life Sciences at the University of Arizona reports that a high-fiber diet can lead to diarrhea. Many fruits have a-high fiber content that can potentially cause you to have diarrhea. One cup of raspberries, for example, has more than 8 grams of fiber, which is about 32 percent of your recommended daily intake of fiber, depending on your gender. If you consume a lot of raspberries or eat them dried in a concentrated form, you might react with a bout of diarrhea. In addition to raspberries, fruits that are notably high in fiber include apples, mangos, apricots, figs, oranges, pears, plums and strawberries, says Everyday Health.


Campylobacter Jejuni Diarrhea Appendicitis Pseudoappendicitis

The Campylobacter genus belongs to the gastrointestinal gram negative rod family of bacteria, and the most renowned species of bacteria under the family is Campylobacter jejuni, a well known cause of pseudoappendicitis, the mimicking of appendicitis without the actual inflammatory reactions taking place at the appendix, accompanied by either bloody or non bloody diarrhea. The epidemiology, pathogenesis, clinical significance, and treatment of Campylobacter jejuni would be discussed in depths in this article.

Animals such as mammals and fowls, both natural and domestic, serve as the primary natural reservoir of Campylobacter. Upon killing of these animals (for example a wild bird) and the consumption of its meat, the bacteria may be transmitted from the animal to human. Since mouth in this case serves as the portal of transmission, this method of spreading is known as the fecal oral route. One should also note that the consumer does not have to eat the meat of the infected animal directly drinking of water contaminated by the infected animal may produce the same cause as well. Thus, the epidemiologic transmission may be either direct or indirect from animals to humans.

The most clinically well recognized manifestation of Campylobacter jejuni is pseudoappendicitis accompanied by either bloody or non bloody diarrhea. Needless to say, the patient experiences acute pain in the right one third of the groins when manifestation becomes pronounced. The point at which the pain is felt is medically termed the McBurney’s Point. This manifestation must be carefully distinguished from that of the bacteria Yersinia Enterocolitica and Pseudotuberculosis, which are manifested by pseudoappendicitis but no diarrhea. Other less specific manifestations of Campylobacter jejuni may include fever and bacteremia. Septic abortion, reactive arthritis, and Guillain Barre syndrome are also some other less clinically important signs of infection.

Campylobacter jejuni may be identified with laboratory techniques such as the culture in microaerophilic medium. Due to the fact that the microorganism require little yet some oxygen for its survival, the culture of one’s stool samples in microaerophilic culturing media may prove effective. Also, the bacteria is also of extremely small size. Utilizing that fact to one’s advantage, a clinician may use a bacteriologic filter for the separation. Thanks to its small size, Campylobacter jejuni should be filtered through the filter, leaving other larger bacteria behind in the stool sample.

The treatment of Campylobacter jejuni should be targeted both against its symptoms and the causative microorganism. The diarrhea requires the replacement of water and electrolyte the failure to do so may result in hypovolemia and possibly its consequent hypovolemic shock. The microorganism is sensitive to many antibiotics, but the drug of choice is ciprofloxacin. In times when such administration is not possible, alternative administration of ampicillin or third generation cephalosporin should be pursued.