Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central ...nervous system-related pathologies, such as Alzheimer's disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites. This influenced plasma concentration of inflammatory cytokines and key metabolic hormones considered therapeutic targets in neurodegeneration. Treated mice showed partial restoration of two impaired neuronal proteolytic pathways (the ubiquitin proteasome system and autophagy). Their cognitive decline was decreased compared with controls, due to a reduction in brain damage and reduced accumulation of amyloid beta aggregates. Collectively, our results clearly prove that modulation of the microbiota induces positive effects on neuronal pathways that are able to slow down the progression of Alzheimer's disease.
Cerebral glucose homeostasis deregulation has a role in the pathogenesis and the progression of Alzheimer's disease (AD). Current therapies delay symptoms without definitively curing AD. We have ...previously shown that probiotics counteract AD progression in 3xTg-AD mice modifying gut microbiota and inducing energy metabolism and glycolysis-gluconeogenesis. Ameliorated cognition is based on higher neuroprotective gut hormones concentrations, reduced amyloid-β burden, and restored proteolytic pathways. Here, we demonstrate that probiotics oral administration improves glucose uptake in 3xTg-AD mice by restoring the brain expression levels of key glucose transporters (GLUT3, GLUT1) and insulin-like growth factor receptor β, in accordance with the diminished phosphorylation of adenosine monophosphate–activated protein kinase and protein-kinase B (Akt). In parallel, phosphorylated tau aggregates decrease in treated mice. Probiotics counteract the time-dependent increase of glycated hemoglobin and the accumulation of advanced glycation end products in AD mice, consistently with memory improvement. Collectively, our data elucidate the mechanism through which gut microbiota manipulation ameliorates impaired glucose metabolism in AD, finally delaying the disease progression.
•SLAB51 restored the brain levels of glucose transporters GLUT3 and GLUT1 in AD mice.•Probiotics administration ameliorated brain glucose homeostasis in AD mice.•Probiotics administration reduced Tau phosphorylation by modulating pAMPK and pAkt.•Advanced glycation end products decreased in probiotics-treated AD mice.•Microbiota modulation counteracts AD progression by affecting glucose homeostasis.
Retrospective analysis of archived tissue samples from bird deaths in the Tuscany region of Italy in 1996 identified Usutu virus. Partial sequencing confirmed identity with the 2001 Vienna strain and ...provided evidence for a much earlier introduction of this virus into Europe than previously assumed.
The endocannabinoid system plays an important role in regulating inflammation in several chronic or anomalous gut inflammatory diseases. In vivo and ex vivo studies showed that 30 days treatment with ...a probiotic mix activated the endocannabinoid system in zebrafish. These results highlight the potential of this probiotic mixture to regulate immune cell function, by inducing gene expression of toll-like receptors and other immune related molecules. Furthermore, TUNEL assay showed a decrease in the number of apoptotic cells, and this finding was supported by a reduction in pro-apoptotic factors and an increase in anti-apoptotic molecules. The results presented here strengthen the molecular mechanisms activated by probiotic mix controlling immune response and inflammation.
Idiopathic inflammatory bowel disease (IBD) is a common chronic enteropathy in dogs. There are no published studies regarding the use of probiotics in the treatment of canine IBD. The objectives were ...to compare responses to treatment with either combination therapy (prednisone and metronidazole) or probiotic strains (VSL#3) in dogs with IBD.
Twenty pet dogs with a diagnosis of IBD, ten healthy pet dogs, and archived control intestinal tissues from three euthanized dogs were used in this open label study. Dogs with IBD were randomized to receive either probiotic (D-VSL#3, n = 10) or combination drug therapy (D-CT, n = 10). Dogs were monitored for 60 days (during treatment) and re-evaluated 30 days after completing treatment. The CIBDAI (P<0.001), duodenal histology scores (P<0.001), and CD3+ cells decreased post-treatment in both treatment groups. FoxP3+ cells (p<0.002) increased in the D-VSL#3 group after treatment but not in the D-CT group. TGF-β+ cells increased in both groups after treatment (P = 0.0043) with the magnitude of this increase being significantly greater for dogs in the D-VSL#3 group compared to the D-CT group. Changes in apical junction complex molecules occludin and claudin-2 differed depending on treatment. Faecalibacterium and Turicibacter were significantly decreased in dogs with IBD at T0, with a significant increase in Faecalibacterium abundance observed in the animals treated with VSL#3 strains.
A protective effect of VSL#3 strains was observed in dogs with IBD, with a significant decrease in clinical and histological scores and a decrease in CD3+ T-cell infiltration. Protection was associated with an enhancement of regulatory T-cell markers (FoxP3+ and TGF-β+), specifically observed in the probiotic-treated group and not in animals receiving combination therapy. A normalization of dysbiosis after long-term therapy was observed in the probiotic group. Larger scale studies are warranted to evaluate the clinical efficacy of VSL#3 in canine IBD.
Aquaculture solid waste (ASW) is a nutrient rich material that can pose a significant environment challenge if not properly managed. This study investigated the potential of black soldier fly (BSF) ...larvae in converting this waste into biomass. Five substrates comprising chicken feed supplemented with varying proportions of fresh ASW (0%, 25%, 50%, 75%, 100%) were formulated and evaluated for larval growth and waste bioconversion efficiency. High nutrients retention (N: 23.25 ± 1.40%; C: 21.94 ± 0.99%; S: 12.20 ± 1.33%) and feed conversion ratio (1.78 ± 0.08) were detected on substrate 100ASW, although the limited feeding rate (114.54 ± 5.38 mg dry substrate/larvae) and the high amount of indigestible fibres (ADF = 15.87 ± 0.24%; ADL = 6.36 ± 0.17%) were translated to low larval growth (final larval average weight: 66.17 ± 1.81 mg). Decreasing ASW content resulted in reduced fibres and ash, increase in non-fibrous carbohydrates and C/N ratio, and improved larval growth and substrate utilization. However, high larval metabolic activity suggested higher nutrients loss to the environment. Substrate 75ASW demonstrated the best performances in terms of larval production (final larval average weight: 176.30 ± 12.12 mg), waste reduction (substrate reduction corrected by percentage of ASW: 26.76 ± 0.86%) and nutrients assimilation (N: 22.14 ± 1.14%; C: 15.29 ± 0.82%; S: 15.40 ± 0.99%). This substrate closely aligned with optimal BSF rearing substrates reported in literature. Overall, this study highlights the potential of BSF larvae in managing fresh ASW, offering a dual benefit of waste reduction and insect biomass production.
The annual fish Nothobranchius furzeri is the shortest-lived vertebrate which can be cultured in captivity. Here, we performed a histopathological analysis of age-related lesions in this species. ...Post-mortem analysis revealed lesions in liver (~90%), kidney (~75%), heart (~70%) and gonads (~40%) which are similar to those previously described in the small teleost Poecilia reticulata. In addition, a high incidence of neoplasias was observed in liver (~35%) and kidney (~25%).
Different laboratory strains of N. furzeri show large genetic differences in longevity. Cross-sectional analysis revealed a clear age-dependent increase in the incidence of liver neoplasias which was accelerated in a short-lived strain. Cross-sectional analysis of gonads revealed sex-specific differences in the occurrence of lesions, with males being more severely affected than females.
In conclusion, our analysis demonstrates that short life span in N. furzeri is a consequence of a typical teleost aging process which determines systemic failure of homeostasis functions rather than of a single organ or apparatus. Unlike other teleosts, however, this scenario is reinforced by high incidence of age-dependent neoplasias, making this species a promising model to analyze the molecular pathways of age-dependent spontaneous tumorigenesis.
► Short life span in Nothobranchius furzeri is a consequence of a typical teleost aging process. ► This scenario is reinforced by high incidence of age-dependent neoplasias. ► This species is a promising model for studies of age-dependent spontaneous tumorigenesis.
Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. ...Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.
Abstract
The aim of this study was to test the effect of mixing doses of glutamate (Glu) and glutamine (Gln) on the growth, health and gut health of post-weaning piglets. One hundred twenty weaned ...piglets (24 ± 2 days of age) were assigned to 6 dietary groups: (1) standard diet (CO); (2) CO plus Glu (6 kg/Ton): 100Glu; (3) CO plus 75Glu + 25Gln; (4) CO plus 50Glu + 50Gln; (5) CO plus 25Glu + 75Gln and (6) CO plus 100Gln. At days 8 and 21, blood was collected for haematological and reactive oxygen metabolite analysis, intestinal mucosa for morphological and gene expression analysis, and caecal content for microbial analysis. Data were fitted using a Generalised Linear Model (GLM). Piglet growth increased linearly with an increase in Gln from d7 to d14. The Glu:Gln ratio had a quadratic effect on faecal consistency and days of diarrhoea, neutrophil% and lymphocyte%, and a positive linear effect on monocyte% in the blood at d8. The amino acids (AAs) reduced the intraepithelial lymphocytes in the jejunum, and 100Gln improved intestinal barrier integrity at d8. The caecal microbiota did not differ. Overall, this study suggested a favourable effect of mixing Glu and Gln (25 + 75–50 + 50) as a dietary supplementation in post-weaning piglets to benefit the immune and barrier function of the gut, resulting in an increase in faecal consistency and improvement of growth during the first 2 weeks post-weaning.
The effects on Giardia duodenalis of Slab51 probiotic supernatants were evaluated in vitro and ex vivo. In vitro, Slab51 (101 UFC) was cultured and the obtained supernatant was filtered, adjusted at ...pH 7, and added (100μl/ml) as such (Slab51 FS) or after heat-treatment, to G. duodenalis cultures to evaluate its effects on G. duodenalis trophozoites growth and adherence. For comparison, negative and metronidazole (20μg/ml) treated controls were used. The morphological and ultrastructural alterations of G. duodenals trophozoites following treatment with Slab51 FS supernatant were investigated by transmission electron microscopy. Ex vivo, mice duodenal portions were cultivated in standard conditions with 5x105 G. duodenalis trophozoites/ml, while to further five duodenal portions similarly cultured and infected, Slab51 FS 200μl was added. After 12 and 18h, samples were fixed in 10% buffered formalin and histologically processed to score Giardia infection and cell damage. Cell proliferation/apoptosis was scored by Ki67, TUNEL and Caspase-3 tests. All experiments were conducted in triplicate throughout the study. All data were statistically evaluated (P< 0.05). Results showed that Slab51 FS significantly reduced Giardia growth and adherence respect to negative controls, but its efficacy was overall lower than that of metronidazole. Moreover, the effects of Slab51 FS were significantly lowered by heat-treatment and this reduction was statistically higher at 90°C than at 56°C, indicating a heat-sensitive nature of active Slab51 FS compounds. At the ultrastructural level, Slab51 FS treated Giardia trophozoites were swelling, increased in size and showed alterations of their cellular membrane and vacuole patterns, loss of the nuclear envelope and nuclear architecture. In ex vivo trials, viable G. duodenalis trophozoites and enterocyte TUNEL+ and Caspase-3 expression were significantly reduced in intestinal sections added with Slab51 FS, while enterocyte Ki67 expression was significantly increased, confirming the anti-G. duodenalis activity of Slab51 FS observed in vitro. In conclusion, results from this study showed that the fresh culture supernatant of the commercial probiotic Slab51 has anti-G. duodenalis properties both in vitro and ex vivo in a mouse model.
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