Oral administration of Simbioflora® (synbiotic) attenuates intestinal damage in a mouse model of 5-fluorouracil-induced mucositis

2018 ◽  
Vol 9 (3) ◽  
pp. 477-486 ◽  
Author(s):  
L.M. Trindade ◽  
V.D. Martins ◽  
N.M. Rodrigues ◽  
E.L.S. Souza ◽  
F.S. Martins ◽  
...  

The use of probiotics to prevent or treat mucosal inflammation has been studied; however, the combined effect of probiotics and prebiotics is unclear. The aim of this study was to test whether oral administration of a synbiotic (Simbioflora®) preparation containing Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus fructooligosaccharide could help control mucosal inflammation in experimental mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly divided into six groups: control (CTL), control + prebiotic (CTL+P), control + synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce mucositis. After 72 h, all mice were euthanised. Intestinal permeability, intestinal histology, and biochemical parameters were analysed. Group MUC showed a greater weight loss and increased intestinal permeability (0.020 counts per min [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P and MUC+S displayed significant recovery of lesions and maintenance of the mucus layer. There were no differences in the short-chain fatty acid concentrations in the faeces between the MUC and CTL groups (P>0.05). Increased acetate and propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S groups. Only the synbiotic treatment increased the butyrate concentration (P<0.05). The results indicate that administration of synbiotic can decrease mucosal damage caused by mucositis.

2021 ◽  
pp. 096032712110588
Author(s):  
Ali Riza Caliskan ◽  
Mehmet Gul ◽  
Ismet Yılmaz ◽  
Baris Otlu ◽  
Nuray Uremis ◽  
...  

Background and Aim The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. Materials and Methods The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. Results Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group ( p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. Conclusion Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.


2021 ◽  
Author(s):  
JooYeon Jhun ◽  
Keun-Hyung Cho ◽  
Dong hwan Lee ◽  
Ji Ye Kwon ◽  
Jin Seok Woo ◽  
...  

Abstract Osteoarthritis (OA) is the most common form of arthritis and age-related degenerative joint disorder, which adversely affects quality of life and causes disability. However, the pathogenesis of OA remains unclear. This study was performed to examine the effects of Lactobacillus rhamnosus in OA progression. OA was induced in 6-week-old male Wistar rats by monosodium iodoacetate (MIA) injection, and the effects of oral administration of L. rhamnosus were examined in this OA rat model. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. The intestines were isolated from OA rats, and the intestinal structure and inflammation were measured. Protein expression in the dorsal root ganglion was analyzed by immunohistochemistry. The effects of L. rhamnosus on mRNA and protein expression in chondrocytes stimulated with interleukin (IL)-1β and lipopolysaccharide (LPS) were analyzed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Pain severity was decreased in L. rhamnosus-treated MIA-induced OA rats. The levels of expression of MCP-1, a potential inflammatory cytokine, and its receptor, CCR2, were decreased, and GABA and PPAR-γ expression were increased in L. rhamnosus-treated OA rats. The inflammation, as determined by IL-1β, and cartilage destruction, as determined by MMP3, were also significantly decreased by L. rhamnosus in OA rats. Intestinal damage and inflammation were also improved by L. rhamnosus. In human OA chondrocytes, TIMP1, TIMP3, SOX9 and COL2A1 which are tissue inhibitors of MMP, and IL-10, an anti-inflammatory cytokine, were increased by L. rhamnosus.L. rhamnosus treatment led to decreased pain severity and cartilage destruction in a rat model of OA. Intestinal destruction and inflammation were also decreased by L. rhamnosus treatment. Our findings suggested the therapeutic potential of L. rhamnosus in OA.


2021 ◽  
Vol 9 (5) ◽  
pp. 1063
Author(s):  
Natalia C. Hernández-Delgado ◽  
Edgar Torres-Maravilla ◽  
Lino Mayorga-Reyes ◽  
Rebeca Martín ◽  
Philippe Langella ◽  
...  

Agave species are a source of diverse products for human use, such as food, fiber, and beverages, which include mezcal, a distilled beverage produced by spontaneous fermentation. Agave is an excellent source of high amounts of sugars, minerals, and phenolic compounds, which favor the growth of lactic acid bacteria (LAB) and yeast communities. In this work, 20 promising LAB strains with probiotic characteristics were isolated from the agave fermentation stage in mezcal production. The strains belonged to Lactobacillus plantarum (15), Lactobacillus rhamnosus (2), Enterococcus faecium (2), and Lactococcus lactis (1). These isolates were characterized for their resistance under gastrointestinal conditions, such as lysozyme, acid pH, and bile salts. In addition, the adherence of these LABs to human intestinal epithelial cells (Caco-2 and HT-29 cells) was tested in vitro and their antioxidant and immunomodulatory profile was determined using cellular models. Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 and LM19 strains were selected for their antioxidant properties, and their capacities in an oxidative stress model in intestinal epithelial cells IECs (Caco-2 and HT-29 cells) in the presence of hydrogen peroxide were evaluated. Interestingly, Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 and LM19 strains showed anti-inflammatory properties in TNF-α-stimulated HT-29 cells. Subsequently, bacterial strains exhibiting antioxidant and anti-inflammatory properties were tested in vivo in a mouse model with dinitrobenzene sulfonic acid (DNBS)-induced chronic colitis. Weight loss, intestinal permeability, and cytokine profiles were measured in mice as indicators of inflammation. One of the selected strains, Lactobacillus plantarum LM17, improved the health of the mice, as observed by reduced weight loss, and significantly decreased intestinal permeability. Altogether, our results demonstrate the potential of LAB (and lactobacilli in particular) isolated from the agave fermentation stage in mezcal production. Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 strains represent potential candidates for developing new probiotic supplements to treat inflammatory bowel disease (IBD).


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1057
Author(s):  
JooYeon Jhun ◽  
Keun-Hyung Cho ◽  
Dong-Hwan Lee ◽  
Ji Ye Kwon ◽  
Jin Seok Woo ◽  
...  

Osteoarthritis (OA) is the most common form of arthritis and age-related degenerative joint disorder, which adversely affects quality of life and causes disability. However, the pathogenesis of OA remains unclear. This study was performed to examine the effects of Lactobacillus rhamnosus in OA progression. OA was induced in 6-week-old male Wistar rats by monosodium iodoacetate (MIA) injection, and the effects of oral administration of L. rhamnosus were examined in this OA rat model. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. The small intestines were isolated from OA rats, and the intestinal structure and inflammation were measured. Protein expression in the dorsal root ganglion was analyzed by immunohistochemistry. The effects of L. rhamnosus on mRNA and protein expression in chondrocytes stimulated with interleukin (IL)-1β and lipopolysaccharide (LPS) were analyzed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Pain severity was decreased in L. rhamnosus-treated MIA-induced OA rats. The levels of expression of MCP-1, a potential inflammatory cytokine, and its receptor, CCR2, were decreased, and GABA and PPAR-γ expression were increased in L. rhamnosus-treated OA rats. The inflammation, as determined by IL-1β, and cartilage destruction, as determined by MMP3, were also significantly decreased by L. rhamnosus in OA rats. Additionally, intestinal damage and inflammation were improved by L. rhamnosus. In human OA chondrocytes, TIMP1, TIMP3, SOX9, and COL2A1 which are tissue inhibitors of MMP, and IL-10, an anti-inflammatory cytokine, were increased by L. rhamnosus. L. rhamnosus treatment led to decreased pain severity and cartilage destruction in a rat model of OA. Intestinal damage and inflammation were also decreased by L. rhamnosus treatment. Our findings suggested the therapeutic potential of L. rhamnosus in OA.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2554
Author(s):  
Marc Micó-Carnero ◽  
Araní Casillas-Ramírez ◽  
Albert Caballeria-Casals ◽  
Carlos Rojano-Alfonso ◽  
Alfredo Sánchez-González ◽  
...  

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sang-Kap Han ◽  
Yeon-Jeong Shin ◽  
Dong-Yeon Lee ◽  
Kyung Min Kim ◽  
Seo-Jin Yang ◽  
...  

Abstract Background Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. Results Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. Conclusions Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.


2012 ◽  
Vol 142 (5) ◽  
pp. S-810 ◽  
Author(s):  
Christophe Vanormelingen ◽  
Tim Vanuytsel ◽  
Tatsuhiro Masaoka ◽  
Hanne Vanheel ◽  
Shadea Salim Rasoel ◽  
...  

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