Evaluation of the Treatment with Akkermansia muciniphila BAA-835 of Chemotherapy-induced Mucositis in Mice.

Mucositis is a high-incidence side effect in cancer patients undergoing chemotherapy. Next-generation probiotics are emerging as new therapeutic tools for managing various disorders. Studies have demonstrated the potential of Akkermansia muciniphila to increase the efficiency of anticancer treatment and to mitigate mucositis. Due to the beneficial effect of A. muciniphila on the host, we evaluated the dose-response, the microorganism viability, and the treatment protocol of A. muciniphila BAA-835 in a murine model of chemotherapy-induced mucositis. Female Balb/c mice were divided into groups that received either sterile 0.9% saline or A. muciniphila by gavage. Mucositis was induced using a single intraperitoneal injection of 5-fluorouracil. The animals were euthanized three days after the induction of mucositis, and tissue and blood were collected for analysis. Prevention of weight loss and small intestine shortening and reduction of neutrophil and eosinophil influx were observed when animals were pretreated with viable A. muciniphila at 1010 colony-forming units per mL (CFU/mL). The A. muciniphila improved mucosal damage by preserving tissue architecture and increasing villus height and goblet cell number. It also improved the integrity of the epithelial barrier, decreasing intestinal permeability and bacterial translocation. In addition, the treatment prevented the expansion of Enterobacteriaceae. The immunological parameters were also improved by decreasing the expression of pro-inflammatory cytokines (IL6, IL1ß, and TNF) and increasing IL10. In conclusion, pretreatment with 1010 CFU/mL of viable A. muciniphila effectively controlled inflammation, protected the intestinal mucosa and the epithelial barrier, and prevented Enterobacteriaceae expansion in treated mice.

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.

Probiogenomics of Leuconostoc Mesenteroides Strains F-21 and F-22 Isolated from Human Breast Milk Reveal Beneficial Properties.

Bacteria of the Leuconostoc genus are Gram-positive bacteria that are commonly found in raw milk and persist in fermented dairy products and plant food. Studies have already explored the probiotic potential of L. mesenteroides, but not from a probiogenomic perspective, which aims to explore the molecular features responsible for their phenotypes. In the present work, probiogenomic approaches were applied in strains F-21 and F-22 of L. mesenteroides isolated from human milk to assess their biosafety at the molecular level and to correlate molecular features with their potential probiotic characteristics. The complete genome of strain F-22 is 1.99 Mb and presents one plasmid, while the draft genome of strain F-21 is 1.89 Mb and presents four plasmids. A high percentage of average nucleotide identity among other genomes of L. mesenteroides (≥ 96%) corroborated the previous taxonomic classification of these isolates. Genomic regions that influence the probiotic properties were identified and annotated. Both strains exhibited wide genome plasticity, cell adhesion ability, proteolytic activity, proinflammatory and immunomodulation capacity through interaction with TLR-NF-κB and TLR-MAPK pathway components, and no antimicrobial resistance, denoting their potential to be candidate probiotics. Further, the strains showed bacteriocin production potential and the presence of acid, thermal, osmotic, and bile salt resistance genes, indicating their ability to survive under gastrointestinal stress. Taken together, our results suggest that L. mesenteroides F-21 and F-22 are promising candidates for probiotics in the food and pharmaceutical industries.

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.

Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.

A Next-Generation Bacteria (Akkermansia muciniphila BAA-835) Presents Probiotic Potential Against Ovalbumin-Induced Food Allergy in Mice.

Next-generation microorganisms have recently gained prominence in the scientific community, mainly due to their probiotic and postbiotic potentials. However, there are few studies that investigate these potentials in food allergy models. Therefore, the present study was designed to evaluate the probiotic potential of Akkermansia muciniphila BAA-835 in an ovalbumin food allergy (OVA) model and also analyse possible postbiotic potential. To access the probiotic potential, clinical, immunological, microbiological, and histological parameters were evaluated. In addition, the postbiotic potential was also evaluated by immunological parameters. Treatment with viable A. muciniphila was able to mitigate weight loss and serum levels of IgE and IgG1 anti-OVA in allergic mice. In addition, the ability of the bacteria to reduce the injury of the proximal jejunum, the eosinophil and neutrophil influx, and the levels of eotaxin-1, CXCL1/KC, IL4, IL6, IL9, IL13, IL17, and TNF, was clear. Furthermore, A. muciniphila was able to attenuate dysbiotic signs of food allergy by mitigating Staphylococcus levels and yeast frequency in the gut microbiota. In addition, the administration of the inactivated bacteria attenuated the levels of IgE anti-OVA and eosinophils, indicating its postbiotic effect. Our data demonstrate for the first time that the oral administration of viable and inactivated A. muciniphila BAA-835 promotes a systemic immunomodulatory protective effect in an in vivo model of food allergy to ovalbumin, which suggests its probiotic and postbiotic properties.

Bifidobacterium longum subsp. longum 51A Attenuates Signs of Inflammation in a Murine Model of Food Allergy.

Food allergy is a pathological condition that can lead to hives, swelling, gastrointestinal distress, cardiovascular and respiratory compromise, and even anaphylaxis. The lack of treatment resources emphasizes the necessity for new therapeutic strategies, and in this way, probiotics has been pointed out as an alternative, especially because of its immunomodulatory properties. The goal of this study was to evaluate the probiotic effect of Bifidobacterium longum subsp. longum 51A (BL51A) in a murine model of ovalbumin (OVA) food allergy, as well as to investigate the effect of the dose and viability of the bacteria on the proposed model. For this purpose, the probiotic effect was assessed by clinical, immunological, and histological parameters in mice treated or not with the BL51A and sensitized or not with OVA. Oral administration of BL51A prevented weight loss and reduced serum levels of IgE anti-OVA and of sIgA in the intestinal fluid. Also, it reduced the intestinal permeability, proximal jejunum damage, recruitment of eosinophils and neutrophils, and levels of eotaxin-1, CXCL1/KC, IL4, IL5, IL6, IL13, and TNF. Furthermore, the treatment was able to increase the levels of IL10. Investigating different doses administered, the level of 108 CFU showed the best results in terms of protective effect. In addition, the administration of the inactivated bacteria did not present any beneficial effect. Results demonstrate that BL51A promotes a systemic immunomodulatory protective effect in a murine model of food allergy that depends on the dose and viability of the bacteria, suggesting its use as probiotic in such disease.

Isolation and Identification of Potential Probiotic Bacteria from Human Milk.

Breast milk was long considered a sterile environment, but now it is known to harbor many bacteria that will shape the newborn microbiota. The benefits of breastfeeding to newborn health are, on some level, related to the presence of beneficial bacteria in human milk. Therefore, this study aims to investigate and isolate potential probiotics present in human milk that might be associated with improved health in infants, being potential candidates to be used in simulated human milk formula. Milk samples of 24 healthy mothers were collected at three time points: 30 min (colostrum), 5-9 days (transitional milk), and 25-30 days (mature milk) postpartum. Samples were evaluated by culturing, and the isolated bacteria were identified by MALDI-TOF MS and 16S DNA sequencing. In vitro screening for probiotics properties was performed, and the potential probiotics were mono-associated with germ-free mice to evaluate their ability to colonize the gastrointestinal tract. The microorganisms were submitted to the spray-drying process to check their viability for a potential simulated milk formula production. Seventy-seven bacteria were isolated from breast milk pertaining to four bacterial genera (Staphylococcus, Streptococcus, Leuconostoc, and Lacticaseibacillus). Four potential probiotics were selected: Lacticaseibacillus rhamnosus (n = 2) and Leuconostoc mesenteroides (n = 2). Isolates were able to colonize the gastrointestinal tract of germ-free mice and remained viable after the spray-drying process. In conclusion, breast milk harbors a unique microbiota with beneficial microorganisms that will impact the newborn gut colonization, being an essential source of probiotic candidates to be used in a formula of simulated maternal milk.

Evaluation of a Functional Craft Wheat Beer Fermented with Saccharomyces cerevisiae UFMG A-905 to treat Salmonella Typhimurium infection in mice.

Functional foods containing probiotics are generally administered as dairy products. Non-dairy beverages are another possibility, but probiotic functionality must be confirmed in such vehicles. In the present study, a craft wheat beer brewed with the probiotic yeast Saccharomyces cerevisiae UFMG A-905 (905) was evaluated in a murine model of Salmonella Typhimurium infection. Unfiltered or filtered beer brewed with 905, a commercial wheat beer used as a negative control, or saline were administered orally to mice before and during oral S. Typhimurium challenge. High fecal levels of yeast were only counted in mice treated with the unfiltered 905 beer, which also had reduced mortality and body weight loss due to S. Typhimurium infection. Increased levels of intestinal IgA, translocation to liver and spleen, liver and intestinal lesions, pro-inflammatory cytokines in liver and ileum, and hepatic and intestinal myeloperoxidase and eosinophilic peroxidase activities were observed in animals infected with S. Typhimurium. All these parameters were reduced by the treatment with unfiltered 905 beer. In conclusion, the results show that a craft wheat beer brewed with S. cerevisiae UFMG A-905 maintained the probiotic properties of this yeast when administered orally to mice challenged with S. Typhimurium.

Dose-Response Effect of Saccharomyces cerevisiae UFMG A-905 on the Prevention of Asthma in an Animal Model.

Probiotics should be administered in adequate amounts to confer health benefits. Probiotic dose-response studies are still missing. Saccharomyces cerevisiae UFMG A-905 prevented asthma development; however, the ideal dose has not been investigated. We evaluated the optimal dose and administration regimen of S. cerevisiae UFMG A-905 in the prevention of asthma. Male Balb/c mice were sensitized intraperitoneally with ovalbumin (OVA) and challenged with OVA intranasally. Mice received, via gavage, daily or alternate-day S. cerevisiae UFMG A-905. In daily regimen, different concentrations (107, 108, or 109 CFU/mL) were given 10 days before OVA sensitization and during challenges. In alternate-day regimen, a concentration of 109 CFU/mL was administered three times per week for 5 weeks, starting 2 weeks prior to the first sensitization. After the last challenge, in vivo bronchial hyperresponsiveness and airway and lung inflammation were assessed. OVA-challenged mice, when compared to saline-challenged mice, presented a significant increase in bronchial hyperresponsiveness and airway and lung inflammation. Daily and alternate-day administration of 109 CFU/mL of S. cerevisiae UFMG A-905 significantly reduced bronchial hyperresponsiveness; lower concentrations of S. cerevisiae UFMG A-905 did not significantly reduce bronchial hyperresponsiveness. Daily regimen with the highest concentration significantly reduced total cell number, eosinophil count in the BAL, and the levels of IL-4, IL-5, and IL-13. Daily administration of S. cerevisiae UFMG A-905 at 107 and 108 CFU/mL and alternate-day regimen did not significantly decrease airway and lung inflammation. S. cerevisiae UFMG A-905 led to a significant attenuation of bronchial hyperresponsiveness and lung inflammation in a dose-dependent manner.

Correction: Interaction of Saccharomyces boulardii with Salmonella enterica Serovar Typhimurium Protects Mice and Modifies T84 Cell Response to the Infection.

[This corrects the article DOI: 10.1371/journal.pone.0008925.].

Bifidobacterium longum subsp. longum 51A attenuates intestinal injury against irinotecan-induced mucositis in mice.

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 51A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 51A at a concentration of 1 × 109 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 51A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 51A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 51A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.

Antarctic Strain of Rhodotorula mucilaginosa UFMGCB 18,377 Attenuates Mucositis Induced by 5-Fluorouracil in Mice.

Mucositis is one of the most strenuous side effects caused by chemotherapy drugs, such as 5-fluorouracil (5-FU), during the treatment of several types of cancers. The disease is so prevalent and aggressive that many patients cannot resist such symptoms. However, despite its frequency and clinical significance, there is no effective treatment to prevent or treat mucositis. Thus, the use of probiotics as an adjuvant for the treatment has gained prominence. In the present study, we evaluated the effectiveness of oral administration of the Antarctic strain of Rhodotorula mucilaginosa UFMGCB 18,377 as an alternative to minimize side effects of 5-FU-induced mucositis in mice. Body weight, food consumption, stool consistency, and presence of blood in the feces were assessed daily in mice orally treated or not with the yeast and submitted or not to experimental mucositis. Blood, bones, and intestinal tissues and fluid were used to determine intestinal permeability and immunological, microbiological, and histopathological parameters. Treatment with R. mucilaginosa UFMGCB 18,377 was able to decrease clinical signs of the disease, such as reduction of food intake and body weight loss, and also decreased the number of intestinal enterobacteria and intestinal length shortening. Additionally, treatment was able to decrease the levels of MPO and EPO activities and inflammatory infiltrates, as well as the histopathological lesions characteristic of mucositis in the jejunum and ileum. Results of the present study showed that the oral administration of R. mucilaginosa UFMGCB 18,377 protected mice against mucositis induced by 5-FU.

Comparative genomics and in silico gene evaluation involved in the probiotic potential of Bifidobacterium longum 51A.

The Bifidobacterium longum 51A strain of isolated from feces of a healthy child, has demonstrated probiotic properties by in vivo and in vitro studies, which may be assigned to its production of metabolites such as acetate. Thus, through the study of comparative genomics, the present work sought to identify unique genes that might be related to the production of acetate. To perform the study, the DNA strain was sequenced using Illumina HiSeq technology, followed by assembly and manual curation of coding sequences. Comparative analysis was performed including 19 complete B. longum genomes available in Genbank/NCBI. In the phylogenetic analysis, the CECT 7210 and 157F strains of B. longum subsp. infantis aggregated within the subsp. longum cluster, suggesting that their taxonomic classification should be reviewed. The strain 51A of B. longum has 26 unique genes, six of which are possibly related to carbohydrate metabolism and acetate production. The phosphoketolase pathway from B. longum 51A showed a difference in acetyl-phosphate production. This result seems to corroborate the analysis of their unique genes, whose presence suggests the strain may use different sources of carbohydrates that allow a greater production of acetate and consequently offer benefits to the host health.

A probiotic has differential effects on allergic airway inflammation in A/J and C57BL/6 mice and is correlated with the gut microbiome.

The phenotypes of allergic airway diseases are influenced by the interplay between host genetics and the gut microbiota, which may be modulated by probiotics. We investigated the probiotic effects on allergic inflammation in A/J and C57BL/6 mice. C57BL/6 mice had increased gut microbiota diversity compared to A/J mice at baseline. Acetate producer probiotics differentially modulated and altered the genus abundance of specific bacteria, such as Akkermansia and Allistipes, in mouse strains. We induced airway inflammation followed by probiotic treatment and found that only A/J mice exhibited decreased inflammation, and the beneficial effects of probiotics in A/J mice were partially due to acetate production. To understand the relevance of microbial composition colonization in the development of allergic diseases, we implanted female C57BL/6 mice with A/J embryos to naturally modulate the microbial composition of A/J mice, which increased gut microbiota diversity and reduced eosinophilic inflammation in A/J. These data demonstrate the central importance of microbiota to allergic phenotype severity. Video Abstract.

In Vitro and In Vivo Evaluation of the Probiotic Potential of Antarctic Yeasts.

Antarctica is one of the most pristine and inhospitable regions of the planet, mostly inhabited by microorganisms that survive due to unusual metabolic pathways to adapt to its extreme conditions, which could be interesting for the selection of new probiotics. The aim of the present study was to screen in vitro and in vivo putative probiotics among 254 yeasts isolated from different habitats of Antarctica. In vitro selection evaluated functional (growth at 37 °C, resistance to simulated gastric environment, and to bile salts), safety (degradation of mucin, production of ß-haemolysis and resistance to antifungal drugs), and beneficial (production of antagonistic substances and adhesion to pathogens) properties. Twelve yeasts were able to grow at 37 °C, one of which was eliminated to present ß-haemolytic ability. The remained yeasts resisted to gastric simulation and bile salts, but none presented antagonism against the pathogens tested. Because of the high co-aggregation with Salmonella enterica Typhimurium and growth yield, Rhodotorula mucilaginosa UFMGCB 18377 and Saccharomyces cerevisiae UFMGCB 11120 were selected for in vivo steps using mice challenged with S. Typhimurium. Both yeasts reached high faecal population levels when daily administered, but only R. mucilaginosa UFMGCB 18377 protected mice against Salmonella infection presenting a higher survival and reduced weight loss, bacterial translocation to the liver, sIgA intestinal levels, and intestinal and hepatic MPO and EPO activities. Our in vitro and in vivo results suggest that R. mucilaginosa UFMGCB 18377 presents probiotic potential and deserve further studies as candidate of probiotic by-products. In addition, this is the first screening study of yeasts isolated from Antarctic environments and of Rhodotorula genus for probiotic use.

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

Characterization of mucosa-associated Escherichia coli strains isolated from Crohn's disease patients in Brazil.

BACKGROUND: Crohn's disease (CD) is characterized by chronic inflammation of the human intestine. Several studies have demonstrated that the intestinal mucosa of CD patients in Western countries is abnormally colonized by adherent-invasive Escherichia coli (AIEC) strains. However, no studies to date have focused on the involvement of such E. coli strains in CD patients in Brazil. Here, we characterized E. coli strains associated with the ileal mucosa of Brazilian CD patients (ileal biopsies from 35 subjects, 24 CD patients and 11 controls). RESULTS: The colonization level of adherent Enterobacteriaceae associated with the ileal mucosa of CD patients was significantly higher than that of the controls. The proportions of E. coli strains belonging to phylogroups B1 and B2 were two-fold higher in strains isolated from CD patients than in those isolated from controls. CD patients in the active phase harbored 10-fold more E. coli belonging to group B2 than CD patients in remission. Only a few E. coli isolates had invasive properties and the ability to survive within macrophages, but 25% of CD patients in Brazil (6/24) harbored at least one E. coli strain belonging to the AIEC pathobiont. However, fimH sequence analysis showed only a few polymorphisms in the FimH adhesin of strains isolated in this study compared to the FimH adhesin of AIEC collections isolated from European patients. CONCLUSIONS: Mucosa-associated E. coli strains colonize the intestinal mucosa of Brazilian CD patients. However, the strains isolated from Brazilian CD patients have probably not yet co-evolved with their hosts and therefore have not fully developed a strong adherent-invasive phenotype. Thus, it will be crucial to follow in the future the emergence and evolution of AIEC pathobionts in the Brazilian population.

Correction to: Genetically engineered probiotic Saccharomyces cerevisiae strains mature human dendritic cells and stimulate gag-specific memory CD8+ T cells ex vivo.

In the Funding section, the following statement is missing: The MACS cohort study was supported by the NIH, National Institute of Allergy and Infectious Diseases grant U01-AI35041.

Treatment with selenium-enriched Saccharomyces cerevisiae UFMG A-905 partially ameliorates mucositis induced by 5-fluorouracil in mice.

PURPOSE: Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice. METHODS: Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination. RESULTS: The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated. CONCLUSIONS: Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.