Project description:Gemcitabine treatment shifts the intestinal microbiota of PC mice towards an inflammatory profile which may worsen mucositis and side effects observed upon chemotherapy. We explored the effect of a specific probiotics blend administered, with or without gemcitabine treatment, to PC xenografted mice.
Project description:The present study was performed to determine if ingesting a blend of probiotics plus amylase would alter the abundance and diversity of gut microbiota in subjects consuming the blend over a 6-week period. 16S and ITS ribosomal RNA (rRNA) sequencing was performed on fecal samples provided by subjects who participated in a clinical study where they consumed either a probiotic amylase blend (Bifidobacterium breve 19bx, Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, and Saccharomyces boulardii 16mxg, alpha amylase (500 SKB (Alpha-amylase-Dextrinizing Units)) or a placebo consisting of rice oligodextrin. The abundance and diversity of both bacterial and fungal organisms was assessed at baseline and following 6 weeks of probiotic amylase blend or placebo consumption. In the subjects consuming the probiotic blend, the abundance of Saccharomyces cerevisiae increased 200-fold, and its prevalence increased (~20% to ~60%) (p ≤ 0.05), whereas the potential pathogens Bacillus thuringiensis and Macrococcus caseolyticus decreased more than 150- and 175-fold, respectively, after probiotic-amylase blend consumption. We also evaluated the correlation between change in microbiota and clinical features reported following probiotic amylase consumption. Nine (9) species (seven bacterial and two fungal) were significantly (negatively or positively) associated with the change in 32 clinical features that were originally evaluated in the clinical study. Oral supplementation with the probiotic-amylase blend caused a marked increase in abundance of the beneficial yeast S. cerevisiae and concomitant modulation of gut-dwelling commensal bacterial organisms, providing the proof of concept that a beneficial commensal organism can re-align the gut microbiota.
Project description:Transferring gut microbiota from one individual to another may enable researchers to "humanize" the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions.
Project description:BackgroundThe gut microbiota is closely associated with the bidirectional gut-brain axis that modulates neuropsychological functions of the central nervous system, thereby affecting mental disorders such as depression. Although it is known that probiotics affect brain functions, the impact of probiotics on the regulation of the prevalence and composition of gut microbiota, leading to anti-depressive effects has not been well understood.MethodsMice were randomly divided into four different groups (n?=?10 for each group) as follows: Group G1 (normal group) as control and group G2 (stress group) were given sterile saline via oral route daily for 8 weeks without and with stress condition, respectively. Under the stress condition, group G3 (fluoxetine group) was administered with fluoxetine hydrochloride and group G4 (probiotic group) was orally given multi-strains of probiotics daily for 8 weeks. After treatment, all mice underwent behavioral testing. Furthermore, fecal samples were collected from randomly selected 5 mice of each group on day 60 and taxonomical analysis of intestinal microbial distribution was performed.ResultsMice subjected to restraint stress showed depressive-like behaviors along with high corticosterone levels in serum. However, probiotic administration alleviated depressive-like behaviors and decreased corticosterone level. Moreover, fecal microbiota was distinctly altered in probiotic-treated mice of the stress group. The relative abundance of phylum and genus levels was significantly decreased in the stress group, but probiotic administration restored the composition of microbes restored.ConclusionIngested probiotics alter the composition of gut microbiota, likely improving the symptoms of depression. Graphical abstract Probiotic administration alters gut microbiota and reduces depressive-like behaviors.
Project description:The modulation of the gut microbiome has been widely suggested as a promising therapeutic strategy for inflammatory bowel disease (IBD). Here, we established a novel probiotic cocktail to investigate its therapeutic role in acute colitis mice. During dextran sulfate sodium (DSS)-induced colitis, the mice were treated with the probiotic cocktail, fecal microbiota transplantation (FMT) from a healthy mice donor, or 5-aminosalicylic acid (5-ASA), respectively. The inflammatory responses were assessed by symptoms, serum inflammatory factors, and histological scoring. The intestinal barrier function was assessed by detecting tight junction proteins. Gut microbiota and its metabolites were further identified using 16S rDNA sequencing and a liquid chromatograph mass spectrometer (LC-MS/MS). Compared with FMT and 5-ASA treatment, the probiotic cocktail performed better in alleviating symptoms of colitis and decreasing disease activity score and mucosal inflammation. The probiotic cocktail also significantly decreased serum IL-17 level and increased JAM-1 expression in colon. The gut microbiota analysis confirmed that the beneficial effects of the probiotic cocktail were attributed to increasing anti-inflammatory bacteria Akkermansia, Bifidobacterium, and Blautia, while decreasing pro-inflammatory bacteria Parasutterella. The targeted metabolome analysis further indicated a rise in the production of Bifidobacterium-related short-chain fatty acids (SCFAs) such as propanoic acid and isobutyric acid after probiotics treatment. Taken together, the probiotic cocktail effectively alleviated intestinal inflammation through improving gut microbiota and metabolites in colitis mice, suggesting its great potential to be a novel therapeutic approach for IBD patients.
Project description:Heavy metal contamination in food endangers human health. Probiotics can protect animals and human against heavy metals, but the detoxification mechanism has not been fully clarified. Here, mice were supplemented with Pediococcus acidilactici strain BT36 isolated from Tibetan plateau yogurt, with strong antioxidant activity but no chromate reduction ability for 20 days to ensure gut colonization. Strain BT36 decreased chromate accumulation, reduced oxidative stress, and attenuated histological damage in the liver of mice. 16S rRNA and metatranscriptome sequencing analysis of fecal microbiota showed that BT36 reversed Cr(VI)-induced changes in gut microbial composition and metabolic activity. Specifically, BT36 recovered the expressions of 788 genes, including 34 inherent Cr remediation-relevant genes. Functional analysis of 10 unannotated genes regulated by BT36 suggested the existence of a new Cr(VI)-reduction gene in the gut microbiota. Thus, BT36 can modulate the gut microbiota in response to Cr(VI) induced oxidative stress and protect against Cr toxicity.
Project description:Diet is one of the most important factors regulating and influencing the composition of our gut microbiome, but the specific effects of commonly used antimicrobial agents i.e., food preservatives present within foods, are not completely understood. In this study, we examined the effect of the three widely used food-grade preservatives i.e., benzoic acid, potassium sorbate, and sodium nitrite, in recommended levels, on the gut microbiota diversity and composition in a mouse model. The analysis of β-diversity reveals distinct signatures of the gut microbiota between mice consuming different preservatives. Further analyses of α-diversity indices also show that the three preservatives induce specific patterns of microbial diversity, with diversity being lowest in mice consuming potassium sorbate. In terms of bacterial abundance, each of the three preservatives demonstrated unique microbial signatures, mainly affecting the proportions of bacterial taxa belonging to Bacteroidetes, Verrucomicrobia, and Proteobacteria. Specifically, we find the increased proportion of Bacteroides, Blautia, Ruminococcus, Oscillospira, and Dorea in mice fed with benzoate; increased abundance of Firmicutes, Turicibacter, and Alkaliphilus by sodium nitrate; and increased proportion of Parabacteroides and Adlercreutzia by potassium sorbate. The findings improve our understanding of how food-grade preservatives may influence the gut microbiota composition and diversity and should facilitate prospective studies investigating diet-microbiome interactions in relation to intestinal and metabolic health.
Project description:Abstract:Background and Aims: We have previously demonstrated that the stage of differentiation of tumors has profound effect on the function of NK cells, and that stem-like/poorly differentiated tumors were preferentially targeted by the NK cells. Therefore, in this study we determined the role of super-charged NK cells in immune mobilization, lysis, and differentiation of stem-like/undifferentiated tumors implanted in the pancreas of humanized-BLT (hu-BLT) mice fed with or without AJ2 probiotics. The phenotype, growth rate and metastatic potential of pancreatic tumors differentiated by the NK cells (NK-differentiated) or patient derived differentiated or stem-like/undifferentiated pancreatic tumors were investigated. Methods: Pancreatic tumor implantation was performed in NSG and hu-BLT mice. Stage of differentiation of tumors was determined using our published criteria for well-differentiated tumors exhibiting higher surface expression of MHC- class I, CD54, and PD-L1 (B7H1) and lower expression of CD44 receptors. The inverse was seen for poorly-differentiated tumors. Results: Stem-like/undifferentiated pancreatic tumors grew rapidly and formed large tumors and exhibited lower expression of above-mentioned differentiation antigens in the pancreas of NSG and hu-BLT mice. Unlike stem-like/undifferentiated tumors, NK-differentiated MP2 (MiaPaCa-2) tumors or patient-derived differentiated tumors were not able to grow or grew smaller tumors, and were unable to metastasize in NSG or hu-BLT mice, and they were susceptible to chemotherapeutic drugs. Stem-like/undifferentiated pancreatic tumors implanted in the pancreas of hu-BLT mice and injected with super-charged NK cells formed much smaller tumors, proliferated less, and exhibited differentiated phenotype. When differentiation of stem-like tumors by the NK cells was prevented by the addition of antibodies to IFN-γ and TNF-α, tumors grew rapidly and metastasized, and they remained resistant to chemotherapeutic drugs. Greater numbers of immune cells infiltrated the tumors of NK-injected and AJ2-probiotic bacteria-fed mice. Moreover, increased IFN-γ secretion in the presence of decreased IL-6 was seen in tumors resected and cultured from NK-injected and AJ2 fed mice. Tumor-induced decreases in NK cytotoxicity and IFN-γ secretion were restored/increased within PBMCs, spleen, and bone marrow when mice received NK cells and were fed with AJ2. Conclusion: NK cells prevent growth of pancreatic tumors through lysis and differentiation, thereby curtailing the growth and metastatic potential of stem-like/undifferentiated-tumors.
Project description:Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder yet it still lacks effective prevention therapies. The aim of this study is to determine whether a novel prebiotic blend (PB) composed of fructo-oligosaccharide (FOS), galactooligosaccharide (GOS), inulin and anthocyanins could be effective in preventing the development of IBS. We explored the possible mechanisms both in animal and in cells. Post-infectious IBS models in C57BL/6 mice were established and were pretreated with the PB, PB and probiotic strains 8 weeks in advance of infection. Eight weeks after infection, intestinal tissues were collected for assessing histomorphology, visceral sensitivity, barrier function, pro-inflammatory cytokines expression and proteomics analysis. Fecal samples were also collected for microbiota analysis. The pro-inflammatory cytokines expression in Caco-2 cells were evaluated after co-incubation with PB and Salmonella typhimurium 14028. The results showed that PB significantly decreased the pro-inflammatory cytokines both in infected Caco-2 cells and PI-IBS models. The loss of body weight, decreased expression of tight junction protein Occludin (OCLN), and changes of the microbiota composition induced by infections could be greatly improved by PB intervention (p < 0.05). The proteomics analysis revealed that this function was associated with Peroxisome proliferator-activated receptor (PPAR)? pathway.