Prebiotic May Help Patients With Intestinal Failure Grow New and Better Gut

Fructooligosaccharides (FOS)

Adding the right prebiotic to the diets of pediatric patients with intestinal failure could replace intravenous feeding, says a new University of Illinois study.

“When we fed the carbohydrate fructooligosacharide (FOS) as a prebiotic, the gut grew and increased in function,” said Kelly A. Tappenden, a U of I professor of nutrition and gastrointestinal physiology. “The study showed that using the correct pre- and probiotic in combination could enhance these results even more.”

When FOS enters the intestines, bacteria convert it into butyrate, a short-chain fatty acid that increases the size of the gut and its ability to digest and absorb nutrients, she said.

But today’s IV solutions don’t contain butyrate and adding it would entail drug development trials and regulatory red tape. She wanted to see if adding this carbohydrate to the diet while continuing to provide most nutrients intravenously would cause the gut to start producing butyrate on its own. It worked.

According to Tappenden, at least 10,000 U.S. patients are totally reliant on intravenous feeding because their intestines have been surgically shortened.

Many of these patients are premature infants who develop necrotizing enterocolitis, a kind of gangrene of the intestine. In the U.S., one in eight infants is a preemie, and removing necrotized, or dead, intestine is the most common surgical emergency in these babies.

“Surgery saves their lives, but with so much intestine removed, they’re unable to digest or absorb nutrients. These babies are also at risk for long-term complications, such as bone demineralization and liver failure. Our goal is to take kids who’ve had this resection and cause their gut to grow and adapt,” she said.

She tested her hypothesis about butyrate using newborn piglets, an excellent model for the human infant in metabolism and physiology. Piglets with intestinal failure were assigned to one of four groups: a control group; a group whose diet contained FOS, a carbohydrate given as a prebiotic to stimulate the production of butyrate by beneficial bacteria; a probiotic, or actual live bacteria; and a combination of pre- and probiotics.

“We believed that bacteria in the gut would use the prebiotic to make butyrate and support intestinal growth. But we thought that might only happen in the group that received both pre- and probiotics because we didn’t know if the newborn gut would have enough bacteria to make this important short-chain fatty acid.”

Actually, the neonatal piglets did have enough bacteria in their guts, and the prebiotic alone was effective in increasing intestinal function and structure, she said.

“In fact, the probiotic that we used in one of the groups eliminated the beneficial effect of the prebiotic. That shows us that we need to be exceptionally careful in selecting the probiotic we use, matching it to the specific disease,” she noted. Many consumers believe all probiotics are equal, but the effect of specific bacterial strains is different, she said.

“At this point, we can only recommend consumption of the FOS prebiotic alone,” she added.

 

Reference 

Barnes JL, Hartmann B, Holst JJ, Tappenden KA. Intestinal adaptation is stimulated by partial enteral nutrition supplemented with the prebiotic short-chain fructooligosaccharide in a neonatal intestinal failure piglet model. JPEN J Parenter Enteral Nutr 2012; 36 (5):  524-37.

Garlic Compound Fights Source of Food-Borne Illness Better Than Antibiotics

Researchers at Washington State University have found that a compound in garlic is 100 times more effective than two popular antibiotics at fighting the Campylobacter bacterium, one of the most common causes of intestinal illness. Their work was published recently in the Journal of Antimicrobial Chemotherapy.

Researchers at Washington State University have found that a compound in garlic is 100 times more effective than two popular antibiotics at fighting the Campylobacter bacterium, one of the most common causes of intestinal illness.

The discovery opens the door to new treatments for raw and processed meats and food preparation surfaces.

“This work is very exciting to me because it shows that this compound has the potential to reduce disease-causing bacteria in the environment and in our food supply,” said Xiaonan Lu, a postdoctoral researcher and lead author of the paper.

“This is the first step in developing or thinking about new intervention strategies,” saif Michael Konkel, a co-author who has been researching Campylobacter jejuni for 25 years.

“Campylobacter is simply the most common bacterial cause of food-borne illness in the United States and probably the world,” Konkel said. Some 2.4 million Americans are affected every year, according to the U.S. Centers for Disease Control and Prevention, with symptoms including diarrhea, cramping, abdominal pain and fever.

The bacteria also are responsible for triggering nearly one-third of the cases of a rare paralyzing disorder known as Guillain-Barré syndrome.

Most infections stem from eating raw or undercooked poultry or foods that have been cross-contaminated via surfaces or utensils used to prepare poultry.

Lu and his colleagues looked at the ability of the garlic-derived compound, diallyl sulfide, to kill the bacterium when it is protected by a slimy biofilm that makes it 1,000 times more resistant to antibiotics than the free floating bacterial cell. They found the compound can easily penetrate the protective biofilm and kill bacterial cells by combining with a sulfur-containing enzyme, subsequently changing the enzyme’s function and effectively shutting down cell metabolism.

The researchers found the diallyl sulfide was as effective as 100 times as much of the antibiotics erythromycin and ciprofloxacin and often would work in a fraction of the time.

Two previous works published last year by Lu and WSU colleagues in Applied and Environmental Microbiology and Analytical Chemistry found diallyl sulfide and other organosulfur compounds effectively kill important food-borne pathogens, such as Listeria monocytogenes and Escherichia coli O157:H7.

Konkel cautioned that the recent work is still at the basic stage, well removed from an actual application. While eating garlic is a generally healthy practice, it is unlikely to prevent Campylobacter-related food poisoning.

However, “diallyl sulfide may be useful in reducing the levels of the Campylobacter in the environment and to clean industrial food processing equipment, as the bacterium is found in a biofilm in both settings,” he said.

“Diallyl sulfide could make many foods safer to eat”, said Barbara Rasco, a co-author on all three recent papers and Lu’s advisor for his doctorate in food science. “It can be used to clean food preparation surfaces and as a preservative in packaged foods like potato and pasta salads, coleslaw and deli meats.”

“This would not only extend shelf life but it would also reduce the growth of potentially bad bacteria,” she said.

 

Reference
Lu X, Samuelson DR, Rasco BA, Konkel ME. Antimicrobial effect of diallyl sulphide on Campylobacter jejuni biofilms. J Antimicrob Chemother. 2012 May 1. [Epub ahead of print]

 

Researchers Show Prebiotic Can Reduce Severity of Colitis

MSU food science and human nutrition researcher Jenifer Fenton

Researchers at Michigan State University have shown a prebiotic may help the body’s own natural killer cells fight bacterial infection and reduce inflammation, greatly decreasing the risk of colon cancer.

Prebiotics are fiber supplements that serve as food for the trillions of tiny bacteria living in the gut. When taken, they can stimulate the growth of the “good” bacteria. The evolution of prebiotic supplements (as well as probiotics, which are actual bacteria ingested into the system) provide new therapeutic targets for researchers and physicians.

In research published in the Journal of Nutrition, MSU’s Jenifer Fenton reports that mice given the prebiotic galacto-oligosaccharide, or GOS, saw the severity of their colitis (one of the main forms of inflammatory bowel disease) significantly reduced.

In fact, the mice fed GOS – a synthetic compound that is known to stimulate beneficial bacteria and is found in foods such as biscuits and infant formula – saw a 50 percent reduction in colitis.

Research has shown certain types of foods and fibers can reduce colon cancer risk, said Fenton of the Department of Food Science and Human Nutrition.

“There is something unique about certain types of fibers, such as GOS, and how they alter cells and influence the immune system to change disease risk, either for the good or bad,” she said. “Our overall goal is to identify either dietary patterns or diet components to reduce inflammation and cancer risk.

“In this case, we used prebiotics to stimulate changes in bacteria in the gut that may have a beneficial impact on the colon.”

Fenton worked closely on the project with Elizabeth Gardner, also with the Department of Food Science and Human Nutrition and who previously has looked at the impact diet plays in fighting off the flu. In applying some of the lessons learned in those studies to mice with bacterially induced colitis, the researchers found mice given GOS had significantly less inflammation and fewer abnormal cells, two precursors for colon cancer.

It appeared, Fenton said, the positive results were linked to the significant enhancement of the body’s own natural killer cells, found in the immune system and crucial in fighting off new infections in the body.

“Our results suggest GOS may be effective in reducing colitis severity by priming the innate immune system,” she said.

The next step is to verify how that mechanism works; finding that link could help researchers apply the lessons learned to other intestinal ailments.

 

References

Gopalakrishnan A, Clinthorne JF, Rondini EA, McCaskey SJ, Gurzell EA, Langohr IM, Gardner EM, Fenton JI. Supplementation with Galacto-Oligosaccharides Increases the Percentage of NK Cells and Reduces Colitis Severity in Smad3-Deficient Mice. 2012 Apr 11. [Epub ahead of print]

Department of Food Science & Human Nutrition, Michigan State University (06.06.2012)

 

How Probiotic Bacteria Protect Against Inflammatory Bowel Diseases

A glimpse through the laser microscope – green indicates the presence of inflammatory messenger substances (chemokines) in the bowel tissue. Picture: TUM

Some lactic acid bacteria can alleviate inflammation and therefore prevent intestinal disorders. Scientists have now decoded the biochemical mechanism that lies behind the protective effect of the bacteria. In experiments with mice, the researchers succeeded in demonstrating that lactocepin – an enzyme produced by certain lactic acid bacteria – selectively degrades inflammatory mediators in diseased tissue. This new evidence might lead to new approaches for the treatment of inflammatory bowel diseases.

Yoghurt has been valued for centuries for its health-promoting effects. These effects are thought to be mediated by the lactic acid bacteria typically contained in yoghurt. Evidence from recent scientific studies show that some bacterial strains actually have a probiotic effect and can thus prevent disease. A team of biologists and nutrition scientists working with Prof. Dirk Haller from the Technische Universitaet Muenchen (TUM) has now discovered the mechanisms at work behind this protective effect (Cell Host & Microbe).

In experiments with mice, the scientists observed that lactocepin – an enzyme produced from the lactic acid bacterium Lactobacillus paracasei – can selectively interrupt inflammatory processes. As the scientists observed, lactocepin degrades messengers from the immune system, known as chemokines, in the diseased tissue. As a part of the “normal” immune response, chemokines are needed to guide defense cells to the source of the infection. In chronic intestinal disorders like Crohn’s disease and ulcerative colitis, the otherwise highly effective defense mechanism against infectious agents is malfunctioning. Chemokines such as “IP-10” then contribute to the tissue damage due to chronic inflammatory processes,  preventing the tissue from healing.

“Lactocepin is a familiar element in food technology research,” says Prof. Dirk Haller, who holds the Chair for Biofunctionality of Food at the TUM. “What is surprising, however, is its biomedical effect, namely the force with which the enzyme attacks and degrades very specific inflammatory mediators.” Haller is certain that, based on this mechanism, it will be possible to develop new approaches to the targeted prevention and treatment of chronic bowel diseases as well as skin disorders: “The anti-inflammatory effect of lactocepin is limited to specific areas and up to now it has no known side effects.”

The scientist therefore plans to carry out clinical studies in order to test the possible pharmaceutical application of the enzyme. Questions also remain to be answered in relation to the “production” of lactocepin by lactic acid bacteria. Some bacterial strains, such as Lactobacillus paracasei, produce highly potent lactocepins; however, the effectiveness of other microorganisms has not yet been proven. Dirk Haller therefore warns against false promises: “Not every product labeled as ‘probiotic’ actually earns this name.”

Reference 
von Schillde MA, Hörmannsperger G, Weiher M, Alpert CA, Hahne H, Bäuerl C, van Huynegem K, Steidler L, Hrncir T, Pérez-Martínez G, Kuster B, Haller D. Lactocepin Secreted By Lactobacillus Exerts Anti-Inflammatory Effects By Selectively Degrading Proinflammatory Chemokines. Cell Host & Microbe 2012; 11 (4): 387–396.