Evaluation of Safety through Acute and Subacute Tests of Galacto-Oligosaccharide (GOS)
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ABSTRACT:
SUBMITTER: Baek Y
PROVIDER: S-EPMC8531431 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study investigated the suppression of photoaging by galacto-oligosaccharide (GOS) ingestion following exposure to ultraviolet (UV) radiation. To investigate its photoprotective effects, GOS along with collagen tripeptide (CTP) as a positive control was orally administered to hairless mice under UVB exposure for 8 weeks. The water holding capacity, transepidermal water loss (TEWL), and wrinkle parameters were measured. Additionally, quantitative reverse-transcription polymerase chain reaction and Western blotting were used to determine mRNA expression and protein levels, respectively. The GOS or CTP orally-administered group showed a decreased water holding capacity and increased TEWL compared to those of the control group, which was exposed to UVB (CON) only. In addition, the wrinkle area and mean wrinkle length in the GOS and CTP groups significantly decreased. Skin aging-related genes, matrix metalloproteinase, had significantly different expression levels in the CTP and GOS groups. Additionally, the tissue inhibitor of metalloproteinases and collagen type I gene expression in the CTP and GOS groups significantly increased. Oral administration of GOS and CTP significantly lowered the tissue cytokine (interleukin-6 and -12, and tumor necrosis factor-?) levels. There was a significant difference in UVB-induced phosphorylation of JNK, p38, and ERK between the GOS group and the CON group. Our findings indicate that GOS intake can suppress skin damage caused by UV light and has a UV photoprotective effect.
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Project description:Animal digestive systems host microorganism ecosystems, including integrated bacteria, viruses, fungi, and others, that produce a variety of compounds from different substrates with healthy properties. Among these substrates, α-galacto-oligosaccharides (GOS) are considered prebiotics that promote the grow of gut microbiota with a metabolic output of Short Chain Fatty Acids (SCFAs). In this regard, we evaluated Lupinus albus GOS (LA-GOS) as a natural prebiotic using different animal models. Therefore, the aim of this work was to evaluate the effect of LA-GOS on the gut microbiota, SCFA production, and intestinal health in healthy and induced dysbiosis conditions (an ulcerative colitis (UC) model). Twenty C57BL/6 mice were randomly allocated in four groups (n = 5/group): untreated and treated non-induced animals, and two groups induced with 2% dextran sulfate sodium to UC with and without LA-GOS administration (2.5 g/kg bw). We found that the UC treated group showed a higher goblet cell number, lower disease activity index, and reduced histopathological damage in comparison to the UC untreated group. In addition, the abundance of positive bacteria to butyryl-CoA transferase in gut microbiota was significantly increased by LA-GOS treatment, in healthy conditions. We measured the SCFA production with significant differences in the butyrate concentration between treated and untreated healthy groups. Finally, the pH level in cecum feces was reduced after LA-GOS treatment. Overall, we point out the in vivo health benefits of LA-GOS administration on the preservation of the intestinal ecosystem and the promotion of SCFA production.
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Project description:Aloe vera has been widely used in health and nutritional supplements in Chinese herbal medicine. Furthermore, Aloe vera production has been an emerging industry for making cosmetics and functional food. However, the reported adverse effects raised questions as to whether Aloe vera and its products were safe enough to be used in medicine and health care. In view of this, the safety evaluation of Aloe vera products before marketing is very important. The present study aimed to assess the toxicological profile of Aloe vera soft capsule (ASC), through acute, subacute toxicity and genotoxicity tests. Male and female ICR mice were received by oral gavage 15000 mg/kg bodyweight of ASC in the acute toxicity test. Male and female SD rats were fed on diet blended with different doses of ASC (equivalent to 832.5, 1665 and 3330 mg/kg bodyweight of ASC) for the subacute toxicity test. In the acute toxicity study, no mortality or behavioral changes were observed, indicating the LD50 was higher than 15000 mg/kg bodyweight. In the subacute toxicity test, no significant changes were observed in bodyweight, food consumption, hematological, biochemical or histopathological parameters in the rats exposed. These data suggested that ASC used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 3330 mg/kg bodyweight. In the genotoxicity study, ASC showed no mutagenic activity in the Ames test and no evidence of potential to induce bone marrow micronucleus or testicular chromosome aberrations in ICR mice exposed to 10000 mg/kg bodyweight. Collectively, ASC could be considered safe before it was marketed as a laxative and moistening health food.
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Project description:Several Lactobacillus plantarum strains are marketed as probiotics for their potential health benefits. Prebiotics, e.g., galacto-oligosaccharides (GOS), have the potential to selectively stimulate the growth of L. plantarum probiotic strains based on their phenotypic diversity in carbohydrate utilization, and thereby enhance their health promoting effects in the host in a strain-specific manner. Previously, we have shown that GOS variably promotes the strain-specific growth of L. plantarum. In this study we investigated this variation by molecular analysis of GOS utilization by L. plantarum. HPAEC-PAD analysis revealed two distinct GOS utilization phenotypes in L. plantarum. Linking these phenotypes to the strain-specific genotypes led to the identification of a lac operon encoding a β-galactosidase (lacA), a permease (lacS), and a divergently oriented regulator (lacR), that are predicted to be involved in the utilization of higher degree of polymerization (DP) constituents present in GOS (specifically DP of 3-4). Mutation of lacA and lacS in L. plantarum NC8 resulted in reduced growth on GOS, and HPAEC analysis confirmed the role of these genes in the import and utilization of higher-DP GOS constituents. Overall, the results enable the design of highly-selective synbiotic combinations of L. plantarum strain-specific probiotics and specific GOS-prebiotic fractions.
| S-EPMC7728778 | biostudies-literature
Project description:Lactose is produced in large amounts as a by-product from the dairy industry. This inexpensive disaccharide can be converted to more useful value-added products such as galacto-oligosaccharides (GOSs) by transgalactosylation reactions with retaining β-galactosidases (BGALs) being normally used for this purpose. Hydrolysis is always competing with the transglycosylation reaction, and hence, the yields of GOSs can be too low for industrial use. We have reported that a β-glucosidase from Halothermothrix orenii (HoBGLA) shows promising characteristics for lactose conversion and GOS synthesis. Here, we engineered HoBGLA to investigate the possibility to further improve lactose conversion and GOS production. Five variants that targeted the glycone (-1) and aglycone (+1) subsites (N222F, N294T, F417S, F417Y, and Y296F) were designed and expressed. All variants show significantly impaired catalytic activity with cellobiose and lactose as substrates. Particularly, F417S is hydrolytically crippled with cellobiose as substrate with a 1000-fold decrease in apparent k cat, but to a lesser extent affected when catalyzing hydrolysis of lactose (47-fold lower k cat). This large selective effect on cellobiose hydrolysis is manifested as a change in substrate selectivity from cellobiose to lactose. The least affected variant is F417Y, which retains the capacity to hydrolyze both cellobiose and lactose with the same relative substrate selectivity as the wild type, but with ~10-fold lower turnover numbers. Thin-layer chromatography results show that this effect is accompanied by synthesis of a particular GOS product in higher yields by Y296F and F417S compared with the other variants, whereas the variant F417Y produces a higher yield of total GOSs.
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Project description:Background and Aims: Lactose intolerance (LI) is a global problem affecting more than half of the world's population. An ultra-purified, high-concentration galacto-oligosaccharide, RP-G28, is being developed as a treatment for patients with LI. The efficacy and safety of RP-G28 in reducing symptoms of lactose intolerance were assessed in a blinded, randomized, placebo-controlled trial. Methods: In this multiclinical site, double-blinded, placebo-controlled trial, 377 patients with LI were randomized to one of two doses of orally administered RP-G28 or placebo for 30 days. A LI test and symptom assessment were performed at baseline and on day 31. The primary endpoint was a ≥4-point reduction or a score of zero on LI composite score on day 31. Voluntary milk and dairy intake and global outcome measures assessed patients' overall treatment satisfaction and quality of life before therapy and 30 days after therapy. This study received Institutional Review Board (IRB) approval. Results: For the primary endpoint, 40% in the RP-G28 groups reported a ≥4-point reduction or no symptoms on LI symptom composite score compared to 26% with placebo (P = 0.016). Treatment with RP-G28 also led to significantly higher levels of milk and dairy intake and significant improvements in global assessments compared to placebo. RP-G28 but not placebo led to significant increases in five Bifidobacterium taxa. Conclusions: RP-G28 for 30 days significantly reduced symptoms and altered the fecal microbiome in patients with LI. Treatment with RP-G28 also improved milk/dairy consumption and quality of life and was safe and well tolerated.
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Project description:Galacto-oligosaccharide (GOS) has been added to infant formula as prebiotics and can bring many benefits to human health. This study proved the effect of GOS in prevention and alleviation against E. coli O157 invasion and colonization and the mechanism behind this was explored in a mice model. The results showed that the expression of Muc2 and Occlaudin were both significantly down-regulated (p < 0.05) by E. coli O157 infection, while GOS alleviated this phenomenon, which means that GOS can reduce the colonization of E. coli O157 by enhancing the gut barrier function. Through the determination of inflammatory cytokines, we found that GOS can relieve inflammation caused by pathogens. At the same time, GOS can promote the growth of probiotics such as Akkermansia, Ruminococcaceae and Bacteroides, thus modulating microorganism environments and improving short chain fatty acid (SCFA) levels in the intestine. This study provides an explanation for the mechanism behind the protection of GOS against pathogen infection.
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Project description:Lactose intolerance, characterized by a decrease in host lactase expression, affects approximately 75% of the world population. Galacto-oligosaccharides (GOS) are prebiotics that have been shown to alleviate symptoms of lactose intolerance and to modulate the intestinal microbiota, promoting the growth of beneficial microorganisms. We hypothesized that mechanisms of GOS utilization by intestinal bacteria are variable, impacting efficacy and response, with differences occurring at the strain level. This study aimed to determine the mechanisms by which human-derived Lactobacillus rhamnosus strains metabolize GOS. Genomic comparisons between strains revealed differences in carbohydrate utilization components, including transporters, enzymes for degradation, and transcriptional regulation, despite a high overall sequence identity (>95%) between strains. Physiological and transcriptomics analyses showed distinct differences in carbohydrate metabolism profiles and GOS utilization between strains. A putative operon responsible for GOS utilization was identified and characterized by genetic disruption of the 6-phospho-β-galactosidase, which had a critical role in GOS utilization. Our findings highlight the importance of strain-specific bacterial metabolism in the selection of probiotics and synbiotics to alleviate symptoms of gastrointestinal disorders including lactose intolerance.
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Project description:The members of the infant microbiome are governed by feeding method (breastmilk vs. formula). Regardless of the source of nutrition, a competitive growth advantage can be provided to commensals through prebiotics - either human milk oligosaccharides (HMOs) or plant oligosaccharides that are supplemented into formula. To characterize how prebiotics modulate commensal - pathogen interactions, we have designed and studied a minimal microbiome where a pathogen, Streptococcus agalactiae engages with a commensal, Streptococcus salivarius. We discovered that while S. agalactiae suppresses the growth of S. salivarius via increased lactic acid production, galacto-oligosaccharides (GOS) supplementation reverses the effect. This result has major implications in characterizing how single species survive in the gut, what niche they occupy, and how they engage with other community members.
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Project description:Unbalanced dietary habits and the consumption of high protein and instant foods cause an increase in constipation. Here, we evaluated the effects of galacto-oligosaccharide (GOS) on a rat model of loperamide-induced constipation by measuring various biological markers and cecal microbiota. The fecal water content and intestinal transit ratio significantly increased in the GOS-administered (GL and GH) groups than in the control group (p < 0.05, p < 0.01, and p < 0.001, respectively). The length of intestinal mucosa (p < 0.05 and p < 0.01, respectively) and area of crypt cells were (p < 0.01, both) significantly increased in the GOS-administered groups compared to the control group. The distribution of interstitial cells of Cajal, which is related to the intestinal movement, showed a significant increase in GOS-administered groups than in the control group (p < 0.01, both). The relative abundance of lactic acid bacteria (LAB), especially Lactobacillus and Lactococcus, significantly increased in the GL group than in the control group. Furthermore, there was a positive correlation between short chain fatty acids (SCFAs) and the gut microbiota in the GL groups. These results demonstrated that GOS administration effectively alleviates constipation by increasing LAB proliferation in the intestinal microbiota and SCFA production.
| S-EPMC7711924 | biostudies-literature