Intestinal Yeast Research Articles

Gut yeast diversity of Helicoverpa armigera (Lepidoptera: Noctuidae) under different dietary conditions.

Yeast is one of the important symbiotic flora in the insect gut. However, little is known about the gut yeast in Helicoverpa armigera (Lepidoptera: Noctuidae) under various dietary conditions. The composition and function of the intestinal yeast community also remain unclear. In this research, we explored the composition of yeast microorganisms in H. armigera larvae under different feeding environments, including apple, pear, tomato, artificial diet (laboratory feeding), Urtica fissa, Helianthus annuus, and Zinnia elegans (wild environment) using high-throughput sequencing. Results showed that a total of 43 yeast OTU readings were obtained, comprising 33 yeast genera and 42 yeast species. The yeast genera with a total content of more than 5% were Hanseniaspora (36.27%), Moesziomyces (21.47%), Trichosporon (16.20%), Wickerhamomyces (12.96%) and Pichia (6.38%). Hanseniaspora was predominant when fed indoors with fruits, whereas Moesziomyces was only detected in the wild group (Urtica fissa, Helianthus annuus, Zinnia elegans) and the artificial diet group. After transferring the larvae from artificial diet to apple, pear and tomato, the composition of intestinal yeast community changed, mainly reflected in the increased relative abundance of Hanseniaspora and the decreased abundance of Trichosporon. Simultaneously, the results of α diversity index indicated that the intestinal yeast microbial diversity of H. armigera fed on wild plants was higher than that of indoor artificial feeding. PCoA and PERMANOVA analysis concluded that there were significant differences in the gut yeast composition of H. armigera larvae on different diets. Our results confirmed that gut yeast communities of H. armigera can be influenced by host diets and may play an important role in host adaptation.

A Clinical Study Provides the First Direct Evidence That Interindividual Variations in Fecal β-Lactamase Activity Affect the Gut Mycobiota Dynamics in Response to β-Lactam Antibiotics.

Antibiotics disturb the intestinal bacterial microbiota, leading to gut dysbiosis and an increased risk for the overgrowth of opportunistic pathogens. It is not fully understood to what extent antibiotics affect the fungal fraction of the intestinal microbiota, the mycobiota. There is no report of the direct role of antibiotics in the overgrowth in healthy humans of the opportunistic pathogenic yeast Candida albicans. Here, we have explored the gut mycobiota of 22 healthy subjects before, during, and up to 6 months after a 3-day regimen of third-generation cephalosporins (3GCs). Using ITS1-targeted metagenomics, we highlighted the strong intra- and interindividual diversity of the healthy gut mycobiota. With a specific quantitative approach, we showed that C. albicans prevalence was much higher than previously reported, with all subjects but one being carriers of C. albicans, although with highly variable burdens. 3GCs significantly altered the mycobiota composition and the fungal load was increased both at short and long term. Both C. albicans relative and absolute abundances were increased but 3GCs did not reduce intersubject variability. Variations in C. albicans burden in response to 3GC treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a high increase of β-lactamase activity displaying a lower increase of C. albicans levels. A same antibiotic treatment might thus affect differentially the gut mycobiota and C. albicans carriage, depending on the treated subject, suggesting a need to adjust the current risk factors for C. albicans overgrowth after a β-lactam treatment. IMPORTANCE Fungal infections are redoubtable healthcare-associated complications in immunocompromised patients. Particularly, the commensal intestinal yeast Candida albicans causes invasive infections in intensive care patients and is, therefore, associated with high mortality. These infections are preceded by an intestinal expansion of C. albicans before its translocation into the bloodstream. Antibiotics are a well-known risk factor for C. albicans overgrowth but the impact of antibiotic-induced dysbiosis on the human gut mycobiota-the fungal microbiota-and the understanding of the mechanisms involved in C. albicans overgrowth in humans are very limited. Our study shows that antibiotics increase the fungal proportion in the gut and disturb the fungal composition, especially C. albicans, in a subject-dependent manner. Indeed, variations across subjects in C. albicans burden in response to β-lactam treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity. This highlighted a potential new key factor for C. albicans overgrowth. Thus, the significance of our research is in providing a better understanding of the factors behind C. albicans intestinal overgrowth, which might lead to new means to prevent life-threatening secondary infections.

S10.3c Clinical studies provide new insights on the association between the microbiota and host resistance to Candida albicans intestinal colonization

S10.3 The mycobiome characterization: future perspectives or just a trend?, September 24, 2022, 10:30 AM - 12:00 PM Objectives Candida albicans is both a harmless commensal intestinal yeast in healthy individuals and a harmful opportunistic pathogen in immunocompromised patients, causing life-threatening invasive candidiasis. C. albicans intestinal overgrowth is a prerequisite for intestinal translocation, which is at the root of invasive candidiasis. Therefore, to prevent invasive candidiasis in immunocompromised patients, it is necessary to curb intestinal C. albicans overgrowth. However, little is known of the role of bacterial species of the microbiota in dampening C. albicans intestinal colonization.We aimed to decipher the influence of the bacterial and fungal intestinal microbiota on C. albicans gut colonization in healthy individuals in whom their microbiota was modified or not by antibiotic treatment.MethodsWe studied two cohorts of healthy individuals: the first cohort included 22 volunteers for which fecal samples were collected before, during and after a 3-day regimen of third-generation cephalosporin antibiotics. The second cohort gathered 1000 healthy individuals for which a single fecal sample was collected. We quantified C. albicans carriage using a specific quantitative PCR approach. We monitored the antibiotic effect on the composition of the fungal microbiota—the so called mycobiota—in the gut of the individuals up to 180 days post-antibiotic exposure, using both the qPCR data and ITS1 targeted metagenomic. We also monitored the level of fecal β-lactamase activity, which is known to modulate the intensity of post-cephalosporin intestinal dysbiosis. Finally, to identify potential C. albicans inhibiting bacteria, we used MaAsLin2 to search for associations between C. albicans levels and bacterial species abundance, deduced from shotgun metagenomics data obtained from all individuals and annotated at the species level.ResultsA very high level of C. albicans carriage was observed in both cohorts, with a prevalence of 95.2% and 83.1% in the first and second cohort, respectively. Yet, the quantity of C. albicans DNA detected varied greatly between subjects. The mycobiota composition was significantly altered by antibiotics and the fungal load was increased both at short and long term. Particularly, C. albicans abundance was increased but with wide inter-subject variations. A part of these variations was explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a low increase of β-lactamase activity displaying a higher increase of C. albicans levels. Finally, using shotgun metagenomics data, we identified a first set of 50 bacterial and archaeal species whose abundance inversely correlated with C. albicans abundance.ConclusionThese results (1) bring a new understanding of C. albicans overgrowth in healthy individuals, (2) lead to the identification of microbial signatures with a potential key role in controlling C. albicans gut colonization, and finally (3) show for the first time that changes in endogenous fecal β-lactamase activity is a key factor for C. albicans overgrowth in the gut after antibiotic exposure. Taken together, these results open the way for new intervention strategies to curb C. albicans intestinal overgrowth.

Visual Identification of Trichosporon asahii, a Gut Yeast Associated with Obesity, Using an Enzymatic NIR Fluorescent Probe.

Lipase found in the gut microbiota participates in the digestion and absorption of dietary fats. As such, the gut microbiota is involved in the regulation of the host metabolism, affecting the levels of lipids and free fatty acids, ultimately resulting in obesity. In this study, an enzymatic activatable near-infrared fluorescent probe, DDAO-C6, was developed for visually sensing endogenous lipase from gut microbes. Using DDAO-C6, a cultivated intestinal yeast strain was rapidly identified from human feces that exhibited high lipase expression and was identified as Trichosporon asahii Y2. We then determined that the colonization of the gut of mice with T. asahii Y2 increased lipase activity in the digestive tract and promoted obesity and hyperlipidemia when the mice were fed high fat diets. Above all, the present research resulted in a fluorescence visualization tool for the functional investigation of gut microbiota associated with obesity and disorders of lipid metabolism.

1521 Case Series of 5 Patients Detected With Gut Fermentation Syndrome

INTRODUCTION: Gut fermentation syndrome (GFS) is a rare medical phenomenon in which ingestion of carbohydrate meals results in alcohol production through different biochemical pathways. These patients are presumed to have intestinal yeast fermenting carbohydrate to alcohol. This is due to fungi overgrowth in the digestive tract. This can often result in alcohol toxicity without any exogenous alcohol intake. The aim of this study was confirmation and treatment of GFS using a standardized carbohydrate challenge test followed by upper and lower endoscopy to obtain intestinal secretions to detect fungal growth. CASE DESCRIPTION/METHODS: This presents five patients who presented with implications of alcoholism while denying use any exogenous alcoholic beverages. A long detailed history and physical examination was conducted in order to screen these patients whose symptoms were unlikely due to exogenous drinking. All other possible primary causes were ruled out. There are currently no established diagnostic criteria to confirm GFS or treat this condition. We therefore propose the following protocol for this. It was important to make certain that patients with suspected GFS who have elevated blood or breath alcohol levels were not surreptitiously drinking. In our provocative carbohydrate challenge test, we gave the patients 200 g of glucose by mouth after an overnight fast with blood drawn at timed intervals of 0, 1/2, 1, 2, 4, 8, 16, and 24 hours for glucose and blood alcohol levels. This test was aborted early if alcohol levels become elevated in the first few hours. This used algorithm, carbohydrate challenge results and a comparison of all five patients is shown in the Table 1 format. If any elevated serum alcohol was detected without any drinking then these patients were recommended to participate for further testing. Routine laboratory testing and stool microbiome were sent for specification. Upper and lower endoscopy were performed during which secretions were collected for bacterial and fungal cultures along with biopsies to further study. DISCUSSION: Any patient denying alcohol ingestion but who has elevated alcohol levels should be investigated. The earliest symptoms of GFS may be mood changes. Some of the patients were bought to us by a concerned family member. This condition was treated with dietary modifications, antifungal therapy, and probiotic use in our patients. We are only starting to recognize the complexity of this condition and are currently studying more patients using the proposed protocol.

The pre-menstrual syndrome (PMS) treatment is unmasked, and it is simple and safe

The Premenstrual Syndrome PMS is a very common problem for women who still menstruate but the prevention treatment is not commonly understood The surprise is that by treating the most common and vexing of the problems facing these ladies namely the excessive gas and bloating by an agent often prescribed for excessive gas leading to bloating the troublesome features of PMS are also ameliorated The agent recommended is the very safe and almost innocuous nystatin Nilstat copy Mycostatin copy which acts by altering the permeability of the cell wall of intestinal yeast fungi There are hundreds of young ladies who can attest to the effectiveness of this method of helping them lead a PMS free life

Porcine intestinal yeast species, Kazachstania slooffiae, a new potential protein source with favourable amino acid composition for animals.

There is little information about Kazachstania slooffiae which dominates among other yeasts in the pigs' intestine. Therefore, the aims of this study were to characterise the yeast cell contents and to investigate which nitrogen sources, organic acids and alcohols may be utilised or produced by this species. The results showed that, K.slooffiae could use urea, ammonium sulphate, peptides and single amino acids and produce thereby ethanol and formic acid. However, this yeast did not metabolise amino acids, lactic, butyric, propionic and acetic acids as sole carbon source. Using a global metabolite profiling approach employing gas chromatography and high-resolution liquid chromatography mass spectrometry, was found that the amount of peptides and dehydroascorbic acid considerably increased in the fermentation residues after yeast cultivation. It is noteworthy that the cells of K.slooffiae had higher contents of nitrogen and total amino acids (especially lysine) than the cells of nutritional yeast (Saccharomyces cerevisiae). This study indicates that due to potential production of peptides and formic acid in the intestinal tract, K.slooffiae might have an impact on the gut health. Moreover, from a nutritional standpoint, the cells of this yeast can be a good source of protein with useful amino acid composition for animal.

Diet-Induced Alteration of the Murine Intestinal Microbiome Following Antibiotic Ablation

Mouse models of antibiotic-induced ablation of the intestinal microbiome have been used to study the microbiome in health and disease. The fecal microbiomes of mice treated with broad-spectrum antibiotics while being fed different laboratory chows were analyzed by Gram stain, quantitative flow cytometry, bacterial cell culture, next generation sequencing of the V3 regions of the 16S ribosomal RNA (rRNA) gene, microscopy, and sequence analysis of the tuf gene. Noncultivatable gram-positive cocci and cultivatable yeast were the microorganisms most readily detected in feces of antibiotic-treated mice fed a defined diet that utilizes casein as a protein source, maltodextrin 10 and sucrose as sources of carbohydrates, and lard as the major source of fat. High-throughput sequencing of the variable regions of the 16S rRNA gene and tuf gene sequencing identified the major bacterial phylotype as Lactococcus. The mouse chow was heavily laden with noncultivatable Lactococcus, which dominated the intestinal flora after consumption. The microbiome of antibiotic-treated mice fed a grain-based diet (mainly wheat, corn and alfalfa) consisted predominantly of a member of the Enterobacteriaceae identified as Escherichia coli, and yeast was not detected by culture or Gram stain. Appearance of intestinal yeast by culture and Gram stain was dependent on the specific chow, although yeast was not detected by culture or Gram stain in the chow. We conclude that bacteria found in food sources can influence qualitative and quantitative assessments of the fecal microbiome, at least in the context of antibiotic therapy, and potentially confound molecular studies that assess the effects of diet on the intestinal ecology. Not surprisingly, different food sources can influence the microbiome, particularly in the context of antibiotic-mediated ablation of the intestinal microbiome. Whether and how the food-derived dead bacteria alter intestinal physiology needs to be determined.

New insights into the role of the porcine intestinal yeast, Kazachstania slooffiae, in intestinal environment of weaned piglets.

Kazachstania slooffiae is a porcine intestinal yeast whose role in the intestinal environment is largely unexplored. Therefore, the impact of K. slooffiae on growth performance, intestinal microbial metabolites and the microbiota of weaned piglets was investigated in this study. Forty-eight German Landrace pigs were weaned at day 27 or 28 of life and grouped into one control and three treatment groups. During the 5-week experiment, piglets had ad libitum access to feed and water. On days 5, 6 and 7 post weaning, pigs were orally supplemented with either placebo or K.slooffiae cells once a day. Faecal samples collected on days 5-8, 14, 21 and 28 post weaning were used for microbiological and chemical analyses. Between groups, there were no significant differences in the incidence of diarrhoea, pH and growth performance. Total yeasts and K.slooffiae correlated positively with total short-chain fatty acids, acetic, propionic, n-butyric, i-valeric and valeric acids, and negatively with pH. Pyrosequencing of the bacterial intestinal community revealed that K.slooffiae significantly affected the composition of the microbiota. The results of this study suggest that K. slooffiae may play an important role in the porcine digestive system, especially in the critical weaning period.

Nosema ceranae Infection Promotes Proliferation of Yeasts in Honey Bee Intestines.

BackgroundNosema ceranae infection not only damages honey bee (Apis melifera) intestines, but we believe it may also affect intestinal yeast development and its seasonal pattern. In order to check our hypothesis, infection intensity versus intestinal yeast colony forming units (CFU) both in field and cage experiments were studied.Methods/FindingsField tests were carried out from March to October in 2014 and 2015. N. ceranae infection intensity decreased more than 100 times from 7.6 x 108 in March to 5.8 x 106 in October 2014. A similar tendency was observed in 2015. Therefore, in the European eastern limit of its range, N. ceranae infection intensity showed seasonality (spring peak and subsequent decline in the summer and fall), however, with an additional mid-summer peak that had not been recorded in other studies. Due to seasonal changes in the N. ceranae infection intensity observed in honey bee colonies, we recommend performing studies on new therapeutics during two consecutive years, including colony overwintering. A natural decrease in N. ceranae spore numbers observed from March to October might be misinterpreted as an effect of Nosema spp. treatment with new compounds. A similar seasonal pattern was observed for intestinal yeast population size in field experiments. Furthermore, cage experiments confirmed the size of intestinal yeast population to increase markedly together with the increase in the N. ceranae infection intensity. Yeast CFUs amounted to respectively 2,025 (CV = 13.04) and 11,150 (CV = 14.06) in uninfected and N. ceranae-infected workers at the end of cage experiments. Therefore, honey bee infection with N. ceranae supported additional opportunistic yeast infections, which may have resulted in faster colony depopulations.

Protein replacement in practical diets altered gut allochthonous bacteria of cultured cyprinid species with different food habits

As the cheap and sustainable recycled natural resources, intestinal casing meal (ICM) and yeast of monosodium glutamate (YMG) might be alternative protein sources in aquaculture diets. To determine the effects of dietary ICM and YMG on fish growth, feed utilization and gut allochthonous bacteria, 8-week feeding trials were conducted with blunt snout bream (Megalobrama amblycephala, MA; a typical herbivorous cultured fish species in China), black carp (Mylopharyngodon piceus, MP; a typical carnivorous species in China) and gibel carp (Carassius gibelio, CG; a typical omnivorous species in China) with partial or complete replacement of soybean meal by ICM or ICM and YMG mixture. The results indicated that ICM and YMG incorporation had positive effects (P value >0.05) on weight gain and feed conversion rate. The complete replacement altered the gut allochthonous microbiota of gibel carp and black carp (Cs < 0.70). Proteobacteria, Fusobacteria, Firmicutes and uncultured bacteria were predominant bacteria in these fish intestine by DGGE detection. Compared with the control diet group with SBM, intestinal allochthonous bacteria of fishes fed with ICM and YMG were significantly stimulated, such as proteobacterium clone (EF707282.1), Cetobacterium somerae (AB353124) and some Bacillus subtilis dependent on fish species. Based on these results, ICM and YMG have the potential to replace SBM in aqua feed, and altered gut allochthonous bacteria variedly as fish food habitats.

Dietary cyclic dipeptides, apoptosis and psychiatric disorders: A hypothesis

Cyclic dipeptides from food and intestinal yeast cyclic dipeptides may play a role in causing psychiatric disorders such as schizophrenia. From cancer research, cyclic dipeptides such as cyclo (proline–phenylalanine) have been found to activate the pathways of apoptosis and to cause programmed cell death. Activation of such pathways is also thought to be important in causing the neurodevelopmental abnormalities seen in disorders such as schizophrenia and autistic disorder, and also may be important in Alzheimer’s. Cyclic dipeptides are found in foods such as malt and cocoa and beer. The intestinal yeast Candida albicans also synthesizes cyclic dipeptides. These dipeptides may be activating apoptosis pathways throughout fetal development and postnatal development, leading to some of the changes seen in brain in schizophrenia and in other psychiatric disorders. These compounds should be researched further to see if they play a role in causing these brain changes. In addition, these cyclic dipeptides are considered within the larger context of research on amino acids and other cyclic dipeptides in neurotransmission and neurophysiology. A better understanding of the role of these cyclic dipeptides in psychiatric disorders could lead to strategies for prevention and treatment of these disorders.

Debaryomyces hansenii and Rhodotorula mucilaginosa comprised the yeast core gut microbiota of wild and reared carnivorous salmonids, croaker and yellowtail

This is the first study using molecular and culture-based methods aimed at investigating the composition of the intestinal yeast microbiota of wild and reared carnivorous salmonids, croaker and yellowtail, to characterize their cores and to evaluate the enzymatic activities of the cultivated yeast. Among 103 samples from salmonids, croaker and yellowtail, yeast were detected in 85.4%, with 43 species identified. The core of reared fish was composed of eight species, in contrast to the wild fish core, which consisted of two species: Debaryomyces hansenii and Rhodotorula mucilaginosa. Despite the smaller diversity of the wild fish core, similar enzymatic profiles were detected for the species from the wild and reared cores. For principal component analysis, samples grouped together independently of host species, domestication status and location. A high proportion of yeast produced aminopeptidases and lipases, which may be explained by the high proportion of protein and lipids in the carnivorous diet. This study reveals the presence of a yeast community in the fish gut that appears to be strongly shaped by a carnivorous diet. Yeast in the gut increases the repertoire of microorganisms interacting with the host intestine, which could influence health and disease.

超微七味白术散对肠道微生物及酶活性的影响

The physiological functions of the human body are influenced by intestinal microbiota.To provide scientific evidence for the clinical effectiveness of ultra-micro decoction pieces of traditional Chinese medicine(specifically the effect of ultra-micro Qiweibaishusan on intestinal microbiota and enzyme activities),mice were rendered dysbacteriotic via administration of antibiotics and then treated with traditional Qiweibaishusan.The effects of the full amount,1/2 the amount,1/4 the amount,and 1/8 amount of ultra-micro Qiweibaishusan on the intestinal microbiota and enzyme activities were analysed.The results showed that the quantities of intestinal microbiota including bacteria,Escherichia coli,yeast,mold,lactobacillus and bifidobacterrium,and the level of xylase activity,protease activity and amylase activity in model group mice were lower than that in control group mice(P0.05).The intestinal cellulase activity in model group mice was higher than that in control group mice(P0.01).The quantities of intestinal bacteria and yeast in traditional Qiweibaishusan group mice were higher than that in control group mice,while intestinal mold was lower(P0.05).The quantity of intestinal yeast increased with the treatment of ultra-micro Qiweibaishusan concentration,while the quantity of intestinal bacteria and mold was highest in the group of mice treated with 1/2 amount of ultra-micro Qiweibaishusan.The quantities of the three categories of intestinal microbiota in the group of mice treated with 1/2 amount of ultra-micro Qiweibaishusan were significantly higher than those in the group of mice treated with the traditional Qiweibaishusan(P0.01).The quantity of Escherichia coli in the groups treated with the traditional Qiweibaishusan and 1/2 amount of ultra-micro Qiweibaishusan reached the normal level(P0.05).The quantity of Escherichia coli in the group mice treated with the whole amount of ultra-micro Qiweibaishusan increased very quickly and was far higher than in the other groups(P0.01).The growth of intestinal lactobacillus and bifidobacterrium could be stimulated by Qiweibaishusan(P0.05).The quantities change of intestinal lactobacillus and bifidobacterium had the same tendency when the model mice were treated with Qiweibaishusan.And the quantities of intestinal lactobacillus and bifidobacterium in the group mice treated with the traditional Qiweibaishusan increased more obviously than which in the control group mice(P0.01).The quantities of intestinal lactobacillus and bifidobacterium in the groups mice treated with ultra-micro Qiweibaishusan were higher than those in the group of mice treated with the traditional Qiweibaishusan(P0.05).And the quantities of intestinal lactobacillus and bifidobacterium in the group treated with 1/2 amount of ultra-micro Qiweibaishusan were far more than that in the other ultra-micro Qiweibaishusan group mice(P0.01).The activity of intestinal cellulase,xylase,protease and amylase showed some correlation to the concentration of Ultra-micro Qiweibaishusan,while the intestinal enzyme activities in the treated mice were lower than that in control group mice(P0.05).The curative effect of 1/2 amount of ultra-micro Qiweibaishusan on dysbacteriotic mice was comparable to the effects presented in traditional Qiweibaishusan group.

Establishment of intestinal microbiota with focus on yeasts of unweaned and weaned piglets kept under different farm conditions

This study aimed to characterize the intestinal yeasts in weaning piglets and to establish their possible relationships with main bacterial groups. German Landrace piglets were weaned (WP, n=32) at 28 days of age or kept with the dams until day 39 without creep feed (UP, n=32). The experiment was performed at an experimental and a commercial farm (CF). Faeces were collected from the piglets, sows and pen floors on days 28, 33 and 39 for isolation of DNA and cultivation for enumeration of yeasts, enterobacteria, enterococci and lactobacilli. Fragments of the D1 domain of 26S rRNA gene were amplified and separated by denaturing gradient gel electrophoresis (DGGE). No yeasts could be cultured from water and feed samples. No or only low numbers of yeasts were detected among all UP. In WP at CF, yeasts correlated with lactobacilli (r=0.456; P=0.009) and enterobacteria (r=-0.407; P=0.021). Kazachstania slooffiae dominated among the cultured yeasts. It was the only yeast species detected by PCR-DGGE. Yeasts, especially K. slooffiae, established in the porcine gastrointestinal tract after consumption of grain-based feed and may interrelate with the intestinal microbiota. The study provides data indicating importance of K. slooffiae for the development of balanced porcine gut microbiota.

Effects of levofloxacin, moxifloxacin and prulifloxacin on murine gut colonization byCandida albicans

Fluoroquinolones are broad-spectrum antibiotics increasingly utilized as empirical or prophylactic therapy in the management of cancer patients. We evaluated the effects of newer generation fluoroquinolones on the level of gastrointestinal (GI) colonization by Candida albicans in a previously established mouse model. Adult male Crl:CD1 (ICR) BR mice were fed chow containing Candida albicans or regular chow. The mice fed the Candida chow had their gut colonized by the yeast. Both groups were subsequently given levofloxacin, moxifloxacin, prulifloxacin or normal saline for 10 days. Stool cultures were performed immediately before, at the end, and one week after discontinuation of treatment to determine the level of intestinal yeast colonization. Candida-colonized mice treated with fluoroquinolones had substantially higher yeast counts in their stools than control mice fed Candida containing chow but treated with saline. Mice fed regular chow and treated with the study antibiotics or saline did not have any Candida in their stools. Dissemination of Candida to internal organs was not observed in any animal. In conclusion, we have shown that all fluoroquinolones tested induced substantial increases in the murine intestinal concentration of C. albicans.

Eradication Is Impossible

“Yeasts in the gut” are a long running topic of interest—a review article in the Deutsches Arzteblatt could form a solid foundation of information. However, the article by Schulze et al does not do justice to the topic. Why might this be so? There are few technical mistakes: data about glucan exposure are cited unilaterally, expression of pathogenicity factors does not enable yeasts to form biofilms. However, a closer look shows that it is suggestive phrases that may result in misunderstandings. Instead of “Candida colonization” the authors refer to “Candida load” [note: in the German original, not the English translation]. Irritable bowel syndrome is described as the indication with the closest—if unconfirmed—similarity to Candida colonization. Rather, it would be correct to state that thus far no clue exists for any such association (1)—and on which basis this is described as a “possible connection” is not clear. The conclusion, “The eradication of intestinal yeasts is advised only for certain clearly defined indications,” is not helpful. However, it still implies that “eradication” may be advised under certain (not precisely defined) circumstances and ignores the fact that this is confirmed not to be possible (1). No new knowledge can be gained from this. The authors ’ remaining “open questions” are not articulated; the “additional facts” that have been “clarified” since 2004 remain obscure. The authors’ activities for Ardeypharm GmbH are correctly reported as a conflict of interests—the committee at the Robert Koch-Institute cites one of the authors (US) as a “protagonist of the Candida hypothesis” (1). This in itself is not reprehensible—the question it raises is that of appropriate and functioning peer review. How could such an article—which is as medically unenlightening as it is highly suggestive—be published in a renowned journal such as Deutsches Arzteblatt?

Yeasts in the Gut

Controversy still surrounds the question whether yeasts found in the gut are causally related to disease, constitute a health hazard, or require treatment. The authors present the state of knowledge in this area on the basis of a selective review of articles retrieved by a PubMed search from 2005 onward. The therapeutic recommendations follow the current national and international guidelines. Yeasts, mainly Candida species, are present in the gut of about 70% of healthy adults. Mucocutaneous Candida infections are due either to impaired host defenses or to altered gene expression in formerly commensal strains. The expression of virulence factors enables yeasts to form biofilms, destroy tissues, and escape the immunological attacks of the host. Yeast infections of the intestinal mucosa are of uncertain clinical significance, and their possible connection to irritable bowel syndrome, while plausible, remains unproved. Yeast colonization can trigger allergic reactions. Mucosal yeast infections are treated with topically active polyene antimycotic drugs. The adjuvant administration of probiotics is justified on the basis of positive results from controlled clinical trials. The eradication of intestinal yeasts is advised only for certain clearly defined indications.

Significance of Urinary Tartaric Acid

In 1995, Shaw et al. (1) reported the gas chromatographic–mass spectrometric identification and quantification of various compounds in the urine of two autistic brothers. In that report (1) and a subsequent one (2), the authors concluded that the presence of several compounds, including tartaric acid (excreted as tartarate), may be causally related to the autistic symptoms and that their origin is an overgrowth of intestinal yeast. The practice of analyzing urine for these compounds to detect intestinal yeast continues, although several lines of evidence contradict these conclusions. Dietary intake is usually the major contributor to urinary tartarate. The US Food and Drug Administration considers it a generally recognized as safe (GRAS) human food ingredient (3). Gram quantities of …

A Novel PDZ Protein Regulates the Activity of Guanylyl Cyclase C, the Heat-stable Enterotoxin Receptor

Secretory diarrhea is the leading cause of infectious diarrhea in humans. Secretory diarrhea may be caused by binding of heat-stable enterotoxins to the intestinal receptor guanylyl cyclase C (GCC). Activation of GCC catalyzes the formation of cGMP, initiating a signaling cascade that opens the cystic fibrosis transmembrane conductance regulator chloride channel at the apical cell surface. To identify proteins that regulate the trafficking or function of GCC, we used the unique COOH terminus of GCC as the "bait" to screen a human intestinal yeast two-hybrid library. We identified a novel protein, IKEPP (intestinal and kidney-enriched PDZ protein) that associates with the COOH terminus of GCC in biochemical assays and by co-immunoprecipitation. IKEPP is expressed in the intestinal epithelium, where it is preferentially accumulated at the apical surface. The GCC-IKEPP interaction is not required for the efficient targeting of GCC to the apical cell surface. Rather, the association with IKEPP significantly inhibits heat-stable enterotoxin-mediated activation of GCC. Our findings are the first to identify a regulatory protein that associates with GCC to modulate the catalytic activity of the enzyme and provides new insights in mechanisms that regulate GCC activity in response to bacterial toxin.