scholarly journals Treatment of Hyperammonemia by Transplanting a Symbiotic Pair of Intestinal Microbes

2022 ◽  
Vol 11 ◽  
Author(s):  
Jing Liu ◽  
Chongkai Zhai ◽  
Jung-Rae Rho ◽  
Sangbum Lee ◽  
Ho Jin Heo ◽  
...  
Keyword(s):  
Chemical Equilibrium ◽  
High Throughput Screening ◽  
Lactobacillus Reuteri ◽  
Therapeutic Option ◽  
Ammonia Level ◽  
Intestinal Lumen ◽  
Blood Ammonia ◽  
Intestinal Microbes ◽  
Therapeutic Mechanism ◽  
Probiotic Strains

Hyperammonemia is a deleterious and inevitable consequence of liver failure. However, no adequate therapeutic agent is available for hyperammonemia. Although recent studies showed that the pharmabiotic approach could be a therapeutic option for hyperammonemia, its development is clogged with poor identification of etiological microbes and low transplantation efficiency of candidate microbes. In this study, we developed a pharmabiotic treatment for hyperammonemia that employs a symbiotic pair of intestinal microbes that are both able to remove ammonia from the surrounding environment. By a radioactive tracing experiment in mice, we elucidated how the removal of ammonia by probiotics in the intestinal lumen leads to lower blood ammonia levels. After determination of the therapeutic mechanism, ammonia-removing probiotic strains were identified by high-throughput screening of gut microbes. The symbiotic partners of ammonia-removing probiotic strains were identified by screening intestinal microbes of a human gut, and the pairs were administrated to hyperammonemic mice to evaluate therapeutic efficacy. Blood ammonia was in a chemical equilibrium relationship with intestinal ammonia. Lactobacillus reuteri JBD400 removed intestinal ammonia to shift the chemical equilibrium to lower the blood ammonia level. L. reuteri JBD400 was successfully transplanted with a symbiotic partner, Streptococcus rubneri JBD420, improving transplantation efficiency 2.3×103 times more compared to the sole transplantation while lowering blood ammonia levels significantly. This work provides new pharmabiotics for the treatment of hyperammonemia as well as explains its therapeutic mechanism. Also, this approach provides a concept of symbiotic pairs approach in the emerging field of pharmabiotics.

scholarly journals Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Chunxu Gao ◽  
Angela Major ◽  
David Rendon ◽  
Monica Lugo ◽  
Vanessa Jackson ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Histidine Decarboxylase ◽  
Model Systems ◽  
Colonic Inflammation ◽  
Histamine H2 Receptor ◽  
Content Type ◽  
Intestinal Microbes ◽  
H2 Receptor ◽  
Probiotic Strains

ABSTRACT Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [18F]fluorodeoxyglucose ([18F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc + L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. IMPORTANCE Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc + L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor-mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics.

scholarly journals Use of design of experiments to optimize the production of microbial probiotic biofilms

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4826 ◽  
Author(s):  
Barbara Speranza ◽  
Arcangelo Liso ◽  
Maria Rosaria Corbo
Keyword(s):  
Design Of Experiments ◽  
Growth Phase ◽  
Lactobacillus Reuteri ◽  
Model Organism ◽  
Cellular Growth ◽  
Effects Of Ph ◽  
Probiotic Strains ◽  
Maximum Cell ◽  
Short Time ◽  
Control Samples

Here, we describe the production of a probiotic biofilm through three intermediate steps: (1) measurement of the adhesion capacity of 15 probiotic strains to evaluate their tendency to form biofilm on different surfaces (stainless steel, glass, and polycarbonate); (2) evaluation of the effects of pH, temperature, cellular growth phase, agitation, and presence of surfactants on probiotic biofilm formation (BF) through the Design of Experiments (DoE) approach; (3) study of the effects of pH, temperature and surfactants concentration on probiotic BF using the Central Composite Design. Finally, we show that biofilms pre-formed by selected probiotics can delay the growth of pathogens, such asListeria monocytogeneschosen as model organism. Among the tested strains,Bifidobacterium infantisDSM20088 andLactobacillus reuteriDSM20016 were found to be as the probiotics able to ensure the greatest adhesion (over 6 Log CFU cm2) to the surfaces tested in a very short time (<24 h). Cellular growth phase and agitation of the medium were factors not affecting BF, pH exerted a very bland effect and a greater tendency to adhesion was observed when the temperature was about 30 °C. The results obtained in the last experimental phase suggest that our probiotic biofilms can be used as an efficient mean to delay the growth ofL. monocytogenes: the λ phase length, in fact, was longer in samples containing probiotic biofilms (0.30–1.02 h) against 0.08 h observed in the control samples. A reduction of the maximum cell load was also observed (6.99–7.06 Log CFU mL−1against about 8 Log CFU mL−1observed in the control samples).

scholarly journals High Blood Ammonia Levels Associated with Long-term Valproic Acids Therapy in Epileptic Children

2020 ◽  
Vol 4 (2) ◽  
pp. 83
Author(s):  
I Gusti Lanang Sidiartha ◽  
I Gusti Ngurah Made Suwarba ◽  
Dyah Kanya Wati ◽  
Ida Bagus Subanada
Keyword(s):  
Valproic Acid ◽  
Combination Therapy ◽  
Ammonia Level ◽  
Blood Ammonia ◽  
Cross Sectional ◽  
Acid Therapy ◽  
Blood Ammonia Level ◽  
Significant Difference ◽  
Epileptic Children

Background: Valproic acid is an effective drug for controlling seizure in children with epilepsy and it is usually used for treatment as long as two years or more. Blood ammonia level often increased in epileptic children who were treated with long-term valproic acid. The study was conducted to determine the relationship between blood ammonia level with valproic acid therapy in epileptic children.Materials and Methods: This is an observational study with cross-sectional approach. The subjects were 64 children with epilepsy, average age of 6.2 years old. Subjects were 33 boys and 31 girls. Blood ammonia level was examined using enzymatic glutamate dehydrogenase. Subjects were divided into 2 therapeutic groups based on the duration, doses and combination therapy of valproic acid. Subjects were recruited from Pediatric Neurology Clinic, Sanglah General Hospital, Bali, Indonesia, from May to December 2017. Comparison of blood ammonia level between groups were analyzed using an Independent t-test with significances if the p<0.05. Results: A significant difference of blood ammonia level was found between subjects who were treated with valproic acid less than 2 years and more than 2 years (45.7±16.4 mmol/L vs. 70.9±43.6 mmol/L; p=0.032). However, significant difference was not found between the groups according to the doses and combination therapy (p=0.450 and p=0.647, respectively).Conclusion: Blood ammonia level was significantly higher in epileptic children who used long-term valproic acid, hence it was recommended to check the blood ammonia level routinely.Keywords: ammonia, epilepsy, valproic, children

Probiotic properties of native Lactobacillus spp. strains for dairy calves

2018 ◽  
Vol 9 (4) ◽  
pp. 613-624 ◽  
Author(s):  
S. Fernández ◽  
M. Fraga ◽  
E. Silveyra ◽  
A.N. Trombert ◽  
A. Rabaza ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
Bacterial Species ◽  
Control Group ◽  
Probiotic Properties ◽  
Real Time Quantitative Pcr ◽  
Treatment And Prevention ◽  
Probiotic Strains ◽  
Lactobacillus Spp

The use of native microorganisms with probiotic capacity is an alternative tool for the treatment and prevention of several diseases that affect animals, such as neonatal calf diarrhoea. The selection of probiotic strains within a collection is based on different in vitro and in vivo assays, which predict their potential. The aim of this study was to characterise a group of native Lactobacillus spp. strains isolated from faeces of healthy calves using an in vitro approach and to assess their ability to colonise the gastrointestinal tract (GIT) of calves. Native Lactobacillus spp. strains were evaluated on their capacity to survive low pH conditions and bile salts presence, biofilm formation and adhesion to both mucus and Caco-2 cells. Based on the in vitro characterisation, four strains (Lactobacillus johnsonii TP1.1, Lactobacillus reuteri TP1.3B, L. johnsonii TP1.6 and Lactobacillus amylovorus TP8.7) were selected to evaluate their capacity to colonise and persist in the GIT of calves. The assessment of enteric persistence involved an in vivo assay with oral administration of probiotics and quantification in faeces of the administered bacterial species with real-time quantitative PCR (qPCR). The study was conducted using 15 calves (1-month-old) which were divided into five groups of three animals, four of which were treated with four different selected strains and one was the control group. Strains TP1.3B and TP1.6 managed to persist in treated animals until ten days after the end of the administration period, indicating that they could be promising candidates for the design of probiotics for calves.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation

Pharmacology ◽  
2018 ◽  
Vol 101 (3-4) ◽  
pp. 156-162
Author(s):  
Yoko Obayashi ◽  
Kenta Kajiwara ◽  
Eiji Nakamura
Keyword(s):  
Beneficial Effect ◽  
Intravenous Infusion ◽  
Ammonia Level ◽  
Glutamine Supplementation ◽  
Glutamic Pyruvic Transaminase ◽  
Elevated Blood ◽  
Blood Ammonia ◽  
Renal Disorder ◽  
Blood Ammonia Level ◽  
Glutamate Oxaloacetic Transaminase

Background: Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. Methods: To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1–4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. Results: Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. Conclusion: These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction.

scholarly journals Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 672 ◽  
Author(s):  
Roberta Affatato ◽  
Laura Carrassa ◽  
Rosaria Chilà ◽  
Monica Lupi ◽  
Valentina Restelli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
High Throughput Screening ◽  
Therapeutic Option ◽  
Xenograft Model ◽  
Antimitotic Drugs ◽  
M Phase ◽  
Sirna Library

Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.

Effects of long-term administration of Lactobacillus reuteri DSM-17938 on circulating levels of 5-HT and BDNF in adults with functional constipation

2019 ◽  
Vol 10 (2) ◽  
pp. 137-147 ◽  
Author(s):  
G. Riezzo ◽  
G. Chimienti ◽  
A. Orlando ◽  
B. D’Attoma ◽  
C. Clemente ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
Functional Constipation ◽  
Probiotic Strain ◽  
Serum Levels ◽  
Double Blind ◽  
Term Administration ◽  
Probiotic Strains ◽  
S Allele ◽  
Item Scores

Accumulated evidence shows that some probiotic strains ameliorate functional constipation (FC) via the modulation of specific gastrointestinal peptide pathways. The aims of this study were to investigate: (1) the effects of long-term administration of Lactobacillus reuteri (LR) DSM 17938 on the serum levels of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF); (2) the possible link between 5-HT, BDNF, and specific constipation-related symptoms; (3) whether genetic variability at the 5-HTT gene-linked polymorphic region (5-HTTLPR) and BDNF Val66Met loci could be associated with serum 5-HT and BDNF variations. LR DSM 17938 was administered to 56 FC patients for 105 days in a randomised, double-blind manner. The fasting blood samples were collected during the randomisation visit (V1), at day 15 (induction period, V2), day 60 (intermediate evaluation, V3), and day 105 (V4) and the Constipaq questionnaire (the sum of Constipation Scoring System (CSS) and patient assessment constipation quality of life (PAC-QoL)) was administered. A group of healthy subjects was enrolled as controls (HC). At V1, the mean serum 5-HT level in the whole patient group was significantly higher (P=0.027) than in HC subjects, while serum BDNF did not. At the end of probiotic administration (V4), 5-HT and BDNF levels were significantly lower than the initial values (V1) (P=0.008 and P=0.015, respectively). 5-HT and BDNF serum concentration were significantly associated (r=0.355; P=0.007). Neither 5-HT nor BDNF serum levels correlated with the CSS item scores and with the PAC-QoL. Lastly, the regression analysis demonstrated that the presence of the S allele of the 5-HTTLPR accounted for the reduction in the 5-HT concentration at V4. In conclusion, the long-term administration of LR DSM 17938 demonstrated that such a probiotic strain could improve FC by affecting 5-HT and BDNF serum concentrations.

scholarly journals The influence of probiotics on the cervical malignancy diagnostics quality

2011 ◽  
Vol 68 (11) ◽  
pp. 956-960 ◽  
Author(s):  
Zivko Perisic ◽  
Natasa Perisic ◽  
Svetlana Golocorbin-Kon ◽  
Dusan Vesovic ◽  
Ana Mitrovic-Jovanovic ◽  
...  
Keyword(s):  
Lactobacillus Reuteri ◽  
False Negative ◽  
Lactobacillus Rhamnosus ◽  
Study Group ◽  
Vaginal Infection ◽  
Cervical Smear ◽  
Vaginal Microflora ◽  
Negative Findings ◽  
Probiotic Strains ◽  
Probiotic Preparation

Background/Aim. Probiotics help to provide an optimum balance in the intestines. Probiotics species competitive block toxic substances and growth of unwanted bacteria and yeast species while they compete for the space and food. Lactogyn? is the first oral probiotics on Serbian market dedicated to maintaining a normal vaginal flora. Lactogyn? contains two well studied probiotics strains - Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Both of them are considered as probiotic agents with therapeutic properties increase the population of beneficial lactobacillus organisms within the vagina. The aim of this study was to exam an influence of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on results of cervical smear cytological testing including detection of atypical cells, detection of false positive and false negative findings as well as on vaginal microflora content in patients with vaginal infection signs and symptoms. Methods. Totally 250 women with signs of vaginal infection were selected to participate in the study. The study group comprised 125 patients taking studied probiotic strains along with specific anti-infective therapy. The control group comprised, also, 125 patients taking anti-infective agents, only. Probiotic preparation (Lactogyn ? capsules) was administered orally (one capsule daily) during 4 weeks. Before and six weeks after beginning of the therapy a cervical smear cytological test (the Papanicolaou test), as well as microbiological examination of the vaginal smear were performed. Results. Number of cases of inflammation and atypical squamous cells of undeterminated significance (ASCUS) in the study group were significantly higher before administration of the probiotic preparation. The number of lactobacilli was significantly higher, and the number of pathogenic microorganisms lower in the group treated with this preparation. Conclusion. The application of probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 concomitantly with specific antiinfective agents provides more reliable cytological diagnostics, reduces the number of false positive and false negative findings on cervical malignancy and normalizes vaginal microflora in higher percentage of patients with vaginal infections comapred with therapy including anti-infective agents only.

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