Approved as a novel food ingredient in Brazil. Extracting trehalose was once a difficult and costly process, but around 2000, the Hayashibara company (Okayama, Japan) discovered an inexpensive extraction technology from starch. It has been confirmed that trehalose is contained in most edible fungi and is an important part of reconstituting dried shiitake mushrooms. Thus, the preponderance of evidence indicates eating foods containing trehalose is safe and will not significantly increase the risk of developing resistant strains of C. difficile (Buckely et al. 2019 & Saund et al. ", "The biosynthesis of trehalose phosphate", "Purification and properties of a novel enzyme, trehalose synthase, from Pimelobacter sp. Collins J., Robinson C., Danhof H., Knetsch C.W., van Leeuwen H.C., Lawley T.D., Auchtung J.M., Britton R.A. WHO/FOA Expert Committee on Food Additive (JECFA). The potential health benefits of trehalose discussed below stem from its ability to [14, 8, 15, 16]: Autophagy is a vital defensive mechanism that removes mutated and damaged cells. Expression of this enzyme in vertebrates is initially found during the gestation period that is the highest after weaning. Authors Anqi Chen 1 , Hugo Tapia 2 , Julie M Goddard 1 , Patrick A Gibney 1 Affiliations 1 Department of Food Science, Cornell University, Ithaca, New York, USA. There is no correlation with importation of trehalose and correlation of epidemic strains of C. diff. Trehalose aqueous solutions show a concentration-dependent clustering tendency. In January of 2018, a paper was published in the journal Nature linking trehalose to a particularly virulent (i.e., infectious) strain of C. difficile (Collins et al. The Examine Database covers Dry Eye. In trehalose, two reducing groups of glucose form a (1,1-glycosidic) bond and thus lose their reducing properties. Find the summary of the lecture 'Trehalose is not associated with the emergence and spread of epidemic Clostridium difficile strains' here. I wonder if they can just call it sugar? Trehalose (from Turkish tgala a sugar derived from insect cocoons + -ose)[3] is a sugar consisting of two molecules of glucose. Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. These results are not surprising. 2021). 000045) to the U.S. Food and Drug Administration (FDA). Because of its stability and functional properties as well as recent innovations in manufacturing, trehalose has become pervasive in sweet and savory foods, e.g., baked goods, frozen desserts, jams and jellies, rice bowls, salads, meat and fish dishes. Does one have to occasionally put up with this kind of nasty surprise after switching to organic beans? How to react to a students panic attack in an oral exam? 2019) examined the potential for trehalose metabolism variants to confer a select advantage for the virulent strains of C. difficile by evaluating how common these variants are within the total genetic diversity of clinical C. difficile using previously sequenced isolates. Eyre and colleagues (Eyre et al. It is also known as mycose or tremalose. Notably, we have known for many years that C. diff infection, whether it occurs or not, is specific to the animal type.. Finally, the majority of existing epidemiological research does not support a valid association between trehalose production/usage and the emergence of resistant strains of C. difficile. 1998;44:787-798. Two molecules of glucose build trehalose, also known as tremalose or mycose. This can occur at lower consumption amounts in a very small percentage of the population having a trehalase deficiency. R48", "Cloning and sequencing of a cluster of genes encoding novel enzymes of trehalose biosynthesis from thermophilic archaebacterium Sulfolobus acidocaldarius", "TreT, a Novel Trehalose Glycosyltransferring Synthase of the Hyperthermophilic Archaeon Thermococcus litoralis*", "Gene expression and molecular characterization of a thermostable trehalose phosphorylase fromThermoanaerobacter tengcongensis", "The Metabolism of ,-Trehalose**The work cited from the author's laboratory was supported by grants from the Robert A. Welch Foundation and the National Institutes of Health (AI 09402). However, one team of scientists questioned the ability of trehalose to enter the cells and induce autophagy. 111 4 Beware of supermarket sushi (as in, not prepared fresh to order) - trehalose is commonly used to keep the rice from staling. 2021). This site is dedicated to helping Their computer says I should see an answer in a few days. Trehalose is a nonreducing sugar formed from two glucose units joined by a 11 alpha bond, giving it the name -D-glucopyranosyl-(11)--D-glucopyranoside. Trehalose is most often used for Other. Between 2000 and 2006, imported levels of trehalose were <1 gram per capita per year in the USA and England, not substantially increasing trehalose intake. Your California Privacy Rights/Privacy Policy. [26] Fifth, trehalose phosphorylase (TreP) either hydrolyses trehalose into glucose-1-phosphate and glucose or may act reversibly in certain species. Online ahead of print. The science around nutrition and food often requires an expert to interpret. The digestion and absorption of trehalose in humans is similar to that of other disaccharides. As a precaution, I'd like to know how to avoid trehalose. Difference between Organic Bread and Fresh Bread. A small percentage of people lack trehalase, an enzyme that breaks down trehalose. WebTrehalose activates autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. Thus, the data reported in this paper does not show that trehalose causes the growth and proliferation of resistant strains of C. difficile in humans. It is important to know that correlation does not equal causation, and in fact, when you look closer at trehalose importation and virulent C. diff out breaks, they do not correlate at all. Relationship between trehalose four-gene cluster presence and 30-day mortality from ribotype-15 (ST10/ST44), There was no evidence for a non-linear relationship between mortality and age using multiple fractional polynomials (, Articles on the Safety of Trehalose as it Relates to, Frontiers in Cellular and Infection Microbiology. Trehalose gained generally recognized as safe (GRAS) status by the U.S. Food and Drug Administration in 2000 and was approved for use in foods in Europe in 2001 (Richards et al. Besides its physical properties used in technology, trehalose may have certain health benefits. If you suspect trehalose intolerance, you may want to avoid mushrooms, seafood, dried and frozen foods. It was able to [24, 25, 26, 27, 28, 29]: Amyotrophic lateral sclerosis (ALS) is a fatal disease that attacks motor neurons and eventually leads to total paralysis. Because it is heat-stable, hydrophilic and resistant to acidic hydrolysis, trehalose has been used a texturizer, stabilizer and occasionally a sweetener in dried foods, frozen foods (e.g., ice cream), nutrition bars, fruit fillings and jams, instant noodles and rice, baked goods and fruit juices (Richards et al. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition. [20]:444, It is commonly used in prepared frozen foods, like ice cream, because it lowers the freezing point of foods. Scandinavian Journal of Gastroenterology. Collins et al. To learn more, see our tips on writing great answers. Trehalose binds water, prevents oxidation, and preserves the structure of food during freezing and heating. It occurs naturally in foods such as mushrooms, honey, shrimp, yeast, and soybeans. Collins J., Robinson C., Danhof H., Knetsch C.W., van Leeuwen H.C., Lawley T.D., Auchtung J.M., Britton R.A. Dietary trehalose enhances virulence of epidemic, Collins J., Danhof H., Britton R.A. Certain strains of C. diff carry a genetic mutation that allow them to, as Prof. Wilcox describes, more effectively metabolize trehalose; breaking trehalose into glucose, and using the glucose as a growth food substance. claimed, by reviewing the genetic code of over 10,000 strains of C. diff for the trehalose metabolizing variant/mutation. Isotrehalose is also yet to be isolated from a living organism, but was found in starch hydroisolates. [36], Trehalose has long been known as an autophagy inducer that acts independently of mTOR. It's called trehalose, and even though its presence in the food chain is nothing new, the amount of it in processed foods is. Trehalose. The metabolism of alpha, alpha-trehalose. How to determine that a particular product is Organic? In test tubes, trehalose induced autophagy in skin tissue. Abbasi J. How do I connect these two faces together? Is it possible for trehalose to be present in an organic certified product? Clostridium difficile causes a type of hospital-acquired infection that is characterized by diarrhea and inflammation of the colon. However, synthetic trehalose was not approved for use in Canada until 2005, and imports to the US did not start increasing until 2007, showing, as Prof. Wilcox described, that its not possible to claim that importation of trehalose was associated with the epidemic of ribotype-027. Trehalose imports postdate the start of the 2003 epidemic by 3 to 4 years and amounts of added trehalose per capita are extremely low compared with naturally occurring intakes of trehalose; this shows that there is no correlation between trehalose imports and the emergence of ribotype-027 and 078 outbreaks. Can I tell police to wait and call a lawyer when served with a search warrant? Safety studies found no adverse effects of trehalose in adults, children, and pregnant women. While the oft-cited association between trehalose production/utilization and C. difficile proliferation may seem compelling, other epidemiological observations suggest that factors besides trehalose consumption may be contributing to the increase in virulent strains of C. difficile (Buckley et al. He goes on to suggest a correlation of these major outbreaks with trehalose imports and use. Trehalose has also been reported for anti-bacterial, anti-biofilm, and anti-inflammatory (in vitro and in vivo) activities, upon its esterification with fatty acids of varying chain lengths. Trehalose may stimulate the growth of Clostridium difficile (C. They should avoid foods and products with trehalose. Is it correct to use "the" before "materials used in making buildings are"? All of our content is written by scientists and people with a strong science background. In addition, data from the U.S. Center for Disease Control (CDC) indicates that at least one of the virulent strains of C. difficile is actually declining, despite the fact that no active measures have been taken to reduce trehalose production or consumption (Abasi 2018). Most of them preferred trehalose over standard eye drops [20, 21]. International and National Authorities Confirm, Approvals of Trehalose Manufactured Using. And that if it can do that, the C. diff strain will be able to outcompete potentially, other C. diff strains and maybe other bacteria if we find C. diff in the human gut.. The authors brought up additional facts that support the potential role of trehalose in recent C. diff. Fortified or enriched. Buckley A.M., Moura I.B., Arai N., Spittal W., Clark E., Nishida Y., Harris H.C., Bentley K., Davis G., Wang D., Mitra S., Higashiyama T., Wilcox M.H. research claims that trehalose imports have played a significant role in the emergence of epidemic strains of C. diff. rev2023.3.3.43278. People with diabetes and insulin resistance should be extra cautious. The results indicated that trehalose metabolism/utilization variants are quite common among the population and supplementation of trehalose did not result in increased levels of C. difficile or its spores compared with glucose or saline supplementation. C. diff infections are on the rise in some countries - both the number and severity of cases and can often be difficult to manage. Sugar, Modified Anystarch, Spices and Flavourings - while they are not necessarily bad for you, they are bad for ingredient disclosure. utilized C. diff ribotype-015; some of the strains in this ribotype carry the metabolic mutation for trehalose metabolism and some do not. Asking for help, clarification, or responding to other answers. The bonding But since it makes C-diff more dangerous, it throws into question its GRAS status. suggests correlation between the increasing importation of synthetic trehalose with a rise in C. diff infection, claiming that the widespread adoption and use of trehalose in the diet coincides with the emergence of both ribotype-027 and 078 outbreaks. As youre about to see in Dangers and Side Effects, its impact on gut bacteria may have a dark side. While it might be a good idea to swap glucose for trehalose, avoid adding it on top of your daily sugar intake. A study by Baylor College of Medicine in Houston found that ingesting trehalose revved up two strains of C-diff "by more than 500-fold," making the bacterium hypervirulent. A procedure developed in 2017 using trehalose allows sperm storage at room temperatures. how is trehalose listed on food labelsvin diesel net worth 2021 forbes. Commonly used as a texturizer, it masks bitterness and food odors, enhances saltiness and highlights fruit flavors. Moreover, growth in vitro in a laboratory setting does not necessarily generalize to a human gut. Researchers examined the effects of trehalose on animal and cellular models of brain-damaging diseases such as Alzheimers, Parkinsons, and Huntingtons disease. Jason A., New York. Trehalose induced autophagy in blood vessel cells and inhibited a virus linked to clogged blood vessels (the human cytomegalovirus or HCMV), but this doesnt tell us much about its potential effects in living organisms [34]. Trehalose shields the cells during freezing (cryoprotection) and thus preserves transplantation organs, stem cells, semen, and different tissue samples [10, 11, 12, 13]. Because of its unique culinary properties, it is also a highly desirable disaccharide used in a variety of food service applications to enhance freshness and flavor. I saw a worrying report of an article in Nature, no less, questioning whether the sugar substitute trehalose could be a cause of the recent rise in Clostridium difficile infections. Trehalose boosted autophagy and prevented r fat buildup in mice with fatty liver. I note that some suppliers purport to sell "organic trehalose". The contents are prepared with the support of Andrea Hardy, Registered Dietitian in Calgary, Canada, in response to the following articles: Nature 553, 285-286 (2018) DOI: https://10.1038/d41586-017-08775-4 EBioMedicine 43 (2019) 347355 DOI: https://doi.org/10.1016/j.ebiom.2019.04.038with the information based on the speech of Prof. Mark H. Wilcox at The 23rd Trehalose Symposium held in Tokyo on 7th November, 2019. This only includes sugars added to products during processing and does not include sugars that occur naturally in fruit and milk. JECFA evaluated the same trehalose information concerning people with trehalase deficiency1. Strains thrived on trehalose, The usually consumed amounts of trehalose are enough to boost their growth, A sharp rise in C. diff. WebTrehalose consists of 2 glucose molecules bound by an ,-1-1 bond. Do roots of these polynomials approach the negative of the Euler-Mascheroni constant? Is it suspicious or odd to stand by the gate of a GA airport watching the planes? Oku T., Okazaki M. Transitory Laxative Threshold of Trehalose and Lactulose in Healthy Women. [31][16] Outbreaks of Clostridium difficile were initially associated with trehalose,[19][32][33] although this finding was disputed in 2019. Trehalose is a sugar which, on a cellular level, appears to have therapeutic mechanisms by regulating protein unfolding. At the top of the Nutrition Facts label, you will find the total number of servings in the container and the food or beverages serving size. that actually disprove this theory. Trehalose is a naturally occurring disaccharide that is readily digested in our guts. In preliminary studies on rats, it prevented ulcers and damage to the stomach lining while maintaining the desired effects [46]. The potential uses of trehalose range from eye care to brain and nerve protection. These strains thrived on trehalose and produced much more toxins [52, 53]. Article 2 The designation "trehalose" shall be displayed on the labelling of the product as such or in the list of ingredients of foodstuffs containing it. However, upon careful analysis, several concerning gaps in the research are identified by Wilcox et al. [25] Fourth, in primitive bacteria, trehalose glycisyltransferring synthase (TreT) produces trehalose from ADP-glucose and glucose. Researchers from Baylor College of Medicine and the University of Oregon have tried to link these two seemingly arbitrary occurrences together in a series of epidemiological and microbiological studies, which has led to media reports and cautionary advice to avoid dietary trehalose (Collins et al. Jan 15, 2018 at 19:02. [7] More research will be needed to confirm the link. Check the ingredients list if whole grains arent in the first three ingredients, the amount is negligible. The only exception is in a specific closely related genetic population, native Greenlanders (Inuits). Inactive Ingredient. For example, Mycobacterium tuberculosis contains trehalose-66-dimycolate (TDM), which triggers inflammation and lung damage in humans [3, 4]. Approved as a novel food in China (Recategorized to a general food in 2018). SelfHacked has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. In summary, we can say with confidence that there is no relationship between the importation and consumption of trehalose in humans and the emergence of epidemic strains of C. diff. 2019). They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again. In bacterial cell wall, trehalose has a structural role in adaptive responses to stress such as osmotic differences and extreme temperature. Sucrose, or common table sugar, is also a non-reducing sugar. Trehalose is a naturally occurring glucose found notably in mushrooms (shiitake, maitake, nameko), sunflower seeds, sea algae, and yeast (bakers, wine). [7], At least three biological pathways support trehalose biosynthesis. Because trehalose is contained in marine plants such as hijiki seaweed, it is called seaweed sugar in China.In fact, trehalose is found in dry yeast, accounting for 12% by dry weight of bakers yeast. Bugs and insects contain plenty of trehalose. If a food contains trehalose, how does it appear in the ingredient list? (36 g) for men and 6 tsp. Looking online at the ingredients in UK supermarket sushi, I see "sugar" added to the rice, but no mention of trehalose. honduras female names; sofitel moorea vs hilton moorea. Scientists have developed a new formulation of aspirin with trehalose that might be gentler on the stomach. Caution: Just like with other simple sugars, you may want to go slow with trehalose because the gut quickly breaks it into 2 glucose molecules. [37] In 2017 research was published showing that trehalose induces autophagy by activating TFEB,[38] a protein that acts as a master regulator of the autophagy-lysosome pathway.[39]. How is it listed as an ingredient? The most common pathway is TPS/TPP pathway which is used by organisms that synthesize trehalose using the enzyme trehalose-6-phosphate (T6P) synthase (TPS). A popular probiotic yeast, S. boulardii, releases trehalase in the gut. Aspirin is a well-known trigger of stomach ulcers, despite modern formulations that may bypass the stomach [45]. Q: I hear there's a new sugar on the market that helps spread a super-strong version of the C-diff infection. Interestingly, Collins et al. [19] Trehalose has about 45% the sweetness of sucrose at concentrations above 22%, but when the concentration is reduced, its sweetness decreases more quickly than that of sucrose, so that a 2.3% solution tastes 6.5 times less sweet as the equivalent sugar solution. In some Webhow is trehalose listed on food labels how is trehalose listed on food labels. Email your health and wellness questions to Dr. Oz and Dr. Roizen at [email protected]. How can I explain to my manager that a project he wishes to undertake cannot be performed by the team? A: You're well-informed, Jason. Hayashibara Co., Ltd., (Hayashibara) manufactures a trehalose product from starch using enzymatic technology and sells it in many countries under the tradename of TREHA. In 2000, FDA approved the sugar as a safe food additive. Trehalose quickly found its way into processed foods in the U.S. and around the world for its mild, flavor-enhancing sweetness and protection of frozen foods. In some store-bought ice creams, its found at concentrations of up to 11 percent. state the ability to metabolize trehalose at lower concentrations confers a competitive growth advantage in the presence of a complex intestinal community, however this was demonstrated in an animal model, which was not repeatable in a proven human model. For this purpose, they make trehalose from corn starch. The glycemic index of trehalose how much it spikes glucose levels compared to sugar is still debated. 2002). Please contact us for information on the regulatory status for any countries of interest. [24] Third, the TreY-TreZ pathway in some bacteria converts starch that contain maltooligosaccharide or glycogen directly into trehalose. rackandboneman. 2022 Oct 6. doi: 10.1111/1541-4337.13048. JECFA Report http://www.inchem.org/documents/jecfa/jecmono/v46je05.htm#_46052320. and other gut infections. (pun intended), For a complete list, see Foods and Products With Trehalose. The lack of strict labeling regulation makes trehalose a bit harder to avoid. One other final experiment in the Nature paper that is worth noting examined the metabolism of trehalose in the intestines of three human subjects consuming their normal diets (which strangely were never described in the paper). He points out that while both strains ribotype-027 and 078 existed prior to 2001, that epidemic outbreaks did not occur until 2003, and include major outbreaks in both Quebec, Canada, and Pittsburgh, USA. Wiggers discovered trehalose in an ergot of rye,[35] and in 1859 Marcellin Berthelot isolated it from Trehala manna, a substance made by weevils and named it trehalose. Thealoz Duo are over-the-counter drops for dry eye containing a combination of trehalose and hyaluronic acid. A large intake of trehalose at one time may induce laxation. It does show that the resistant strains of C. difficile can grow in vitro on low doses of trehalose, but they metabolize and flourish on several other carbon sources as well (and, as noted, none were directly compared to trehalose). Given that most people have trehalase in the gut, these tiny creatures have probably been our staple food throughout evolution [59, 60, 54]. These studies provided a range of low trehalase activity from 0% to a maximum of 2%. How to store organic cold press sunflower oil for long term usage? The food industry recognized these unique properties of trehalose and introduced it as an additive in dried and frozen foods. Trehalose is less soluble than sucrose, except at high temperatures (>80C). Trehalose is a naturally occurring disaccharide made up of two glucose molecules. Click here to learn more and see if youre at risk. More recent research not only contradicts findings from the Nature paper, but refutes a causal connection between trehalose consumption and C. difficile infections. He found a way to merge his two biggest passionswriting and healthand use them for noble purposes. WebTrehalose as specified in the Annex, may be placed on the market in the Community as novel food or novel food ingredient for use in foodstuffs. When scientists noticed the parallel between the epidemic rise of C-diff and trehalose deployment over the past 20 years, they dug deeper. Trehalose is used in foods as a sweetener, a stabilizer and thickener, and a flavor enhancer. disney songs with alliteration; does the fbi honor sealed state records; Stack Exchange network consists of 181 Q&A communities including Stack Overflow, the largest, most trusted online community for developers to learn, share their knowledge, and build their careers. Lastly, Prof. Wilcox and his team set out to describe how C. diff would grow in a human gut model (a triple phase chemostat gut model) when trehalose is administered (as a potential food for the bacteria) in comparison to controls. 00045). [6], Trehalose is a disaccharide formed by a 1,1-glycosidic bond between two -glucose units. Do I need a thermal expansion tank if I already have a pressure tank? In the lightning goddess of death. [11], Trehalose is the major carbohydrate energy storage molecule used by insects for flight. WebTrehalose and its applications in the food industry Compr Rev Food Sci Food Saf. The transitory laxative threshold of trehalose was reported to be 0.65 g/kg-body weight, or 39 g in a 60-kg person2. In healthy and obese mice, trehalose lowered blood insulin spikes and insulin resistance, prevented fat accumulation, and protected the heart from damage [37, 38, 39]. For this reason, dry yeast can be preserved in a dried state without losing fermentative activity. It is often difficult to tell what is accurate in the media when an entire body of evidence is not reviewed. Your email address will not be published. This is unlike ribotype-027 strains, which all appear to have the mutation. reported that a rise in trehalose consumption could explain increased rates of mortality from Clostridium difficile infections. A large intake of trehalose at one time may induce laxation. In addition, the study did not show that eating a normal diet containing trehalose increased levels of C. difficile bacteria in the gut, nor that it caused symptoms; only that it increased the expression of a gene that metabolizes trehalose. By clicking Accept all cookies, you agree Stack Exchange can store cookies on your device and disclose information in accordance with our Cookie Policy. Prof. Wilcox presented his findings at the 2019 Trehalose Symposium in Tokyo, Japan to a group of industry leaders and researchers interested in and working with trehalose, explaining crucial gaps in the Collins et al. Trehalose can bind water and retain moisture, which makes trehalose eye drops a popular choice for dry eye. how is trehalose listed on food labels. Anhydrous forms of trehalose readily regain moisture to form the dihydrate. The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. ", "Brush border membrane sucrase-isomaltase, maltase-glucoamylase and trehalase in mammals. [citation needed] One possible reason for this is that the glycosidic linkage of trehalose, when acted upon by an insect trehalase, releases two molecules of glucose, which is required for the rapid energy requirements of flight. is a clickable link to peer-reviewed scientific studies. It only takes a minute to sign up. No clinical evidence supports the use of trehalose for any of the conditions listed in this section. 1995). It now costs $3 per kilo. 2002). After controlling for all clinical factors independently associated with risk for severe infection outcome, the authors found no significant association between the presence of trehalose utilization variants in infectious C. difficile strains and the development of severe infection outcomes. Joe Cohen flipped the script on conventional and alternative medicine and it worked. View Bacteria, plants, fungi, and insects use it as an energy source and a guard against extreme conditions. WebPure Original Ingredients Trehalose is a natural sweetener Use as a substitute for sugar in drinks & baking Non GMO & Vegan Always pure ingredients with no additives Packaged in Utah, USA Additional Details Small Business This product is from a small business brand. The US Food and Drugs Agency (FDA) labeled trehalose as GRAS (generally recognized as safe) when added to dietary products [48, 49]. The feeding experiment was conducted in a mouse model (which may or may not translate to a human model) and did not include a carbohydrate comparison. outbreaks has occurred shortly after the food industry started using trehalose on a large scale. However, the media recently blamed it for the rise in resistant superbugs. Prof. Wilcox and his team found that there is no association between possession of this trehalose mutant gene metabolism, four-gene cluster, and death, likelihood of death, in humans infected with these strains. We do not aim to diagnose, treat, cure or prevent any illness or disease. It is common among the Inuits from Greenland (approx. In a recent publication covered by the media, Collins et al. [16] In humans, the only known function of trehalose is its ability to activate autophagy inducer. The above study suggests its index is surprisingly low (38) while other studies indicate its borderline high (~70) [40, 41]. For example, in Canada, outbreaks of the virulent strains of C. difficile occurred some three years before the approval and expanded use trehalose.

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