Prebiotic Agent Research Articles

Human Milk Oligosaccharides (HMOs) and Infant Microbiota: A Scoping Review.

Human milk oligosaccharides (HMOs) are the third most abundant solid component of breast milk. However, the newborn cannot assimilate them as nutrients. They are recognized prebiotic agents (the first in the newborn diet) that stimulate the growth of beneficial microorganisms, mainly the genus Bifidobacterium, dominant in the gut of breastfed infants. The structures of the oligosaccharides vary mainly according to maternal genetics, but also other maternal factors such as parity and mode of delivery, age, diet, and nutritional status or even geographic location and seasonality cause different breast milk oligosaccharides profiles. Differences in the profiles of HMO have been linked to breast milk microbiota and gut microbial colonization of babies. Here, we provide a review of the scope of reports on associations between HMOs and the infant gut microbiota to assess the impact of HMO composition.

A homogeneous polysaccharide from Lycium barbarum: Structural characterizations, anti-obesity effects and impacts on gut microbiota

Lycium barbarum polysaccharides (LBPs) are known for their beneficial effects on diabetes, NAFLD and related chronic metabolic diseases induced by high-fat diet (HFD). However, the relevant researches are mainly about the whole crude polysaccharides, the specific active ingredient of LBPs and its bioactivity have been rarely explored. Herein, a homogeneous polysaccharide (LBP-W) was isolated and purified from crude LBPs. Structure characterizations indicated that LBP-W contained a main chain consisting of a repeated unit of →6)-β-Galp(1 → residues with branches composed of α-Araf, β-Galp and α-Rhap residues at position C-3. The objective of this study was to evaluate the anti-obesogenic effect of LBP-W and figure out the underlying mechanisms. In vivo efficacy trial illustrated that LBP-W supplements can alleviate HFD-induced mice obesity significantly. Gut microbiota analysis showed that LBP-W not only improved community diversity of intestinal flora, but also regulated their specific genera. Moreover, LBP-W can increase the content of short-chain fatty acids (SCFAs), a metabolite of the intestinal flora. In summary, all these results demonstrated that the homogeneous polysaccharide purified from L. barbarum could be used as a prebiotic agent to improve obesity by modulating the composition of intestinal flora and the metabolism of SCFAs.

The secondary hyperoxaluria in children: the therapeutic potential of prebiotics and probiotics

The article presents modern data on the use of probiotic and prebiotic drugs to prevent the formation of secondary hyperoxaluria in children. The authors analyzed the literature data and generalized the available results of original studies on the use of probiotics and prebiotics to prevent the development and to reduce the laboratory manifestations of secondary hyperoxaluria by improving the state of the intestinal microflora involved in the degradation of oxalates. They demonstrated the ability of Oxalobacter formigenes, Lactobacillus spp. и Bifidobacterium spp. bacteria to participate in the metabolism of oxalates, to reduce the excretion of oxalates with the urine, thereby reducing the laboratory manifestations of secondary hyperoxaluria. The article shows the therapeutic correction of the disease by improving the state of the intestinal microflora with both probiotic preparations containing Lactobacillus spp. and Bifidobacterium spp. strains and prebiotic agents. The drugs that normalize the state of the intestinal microflora (probiotics and prebiotics) help to rationalize the management of patients with secondary hyperoxaluria and to reduce the manifestations of secondary hyperoxaluria.

Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation

Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut–liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.

Quercetin Ameliorates Gut Microbiota Dysbiosis That Drives Hypothalamic Damage and Hepatic Lipogenesis in Monosodium Glutamate-Induced Abdominal Obesity.

Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.

Metabolic regulation mechanism of fucoidan via intestinal microecology in diseases.

The intestinal microecology is an extremely complex ecosystem consisting of gut microbiota, intestinal mucosa and the intestinal immune system. The intestinal microecology performs several important functions and is considered to be an essential 'organ' because it plays an important role in regulating human metabolism. Fucoidan contains a large amount of fucose and galactose residues, as well as various other neutral and acidic monosaccharides. Fucoidan particularly effects tumors, inflammatory bowel disease, diabetes and obesity by repairing intestinal mucosal damage and improving the intestinal microecological environment. It has been proposed that fucoidan could be used as a prebiotic agent for pharmaceutical and functional foods. In this review, we elucidate the potential mechanisms of the metabolic regulation of fucoidan with respect to the intestinal microecology of diseases. © 2021 Society of Chemical Industry.

Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis.

Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg-1·d-1, po) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1β, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP.

Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation

Ganoderma lucidum has been shown to have anti-obesity effects. However, polysaccharide extracted from the sporoderm-broken spores of Ganoderma lucidum (BSGLP) against obesity and its underlying mechanisms have never been reported. In the current study, we showed that BSGLP inhibited high-fat diet (HFD)-induced obesity, hyperlipidemia, inflammation, and fat accumulation in C57BL/6 J mice. BSGLP improved HFD-induced gut microbiota dysbiosis, maintained intestinal barrier function, increased short-chain fatty acids production and GPR43 expression, ameliorated endotoxemia, manifested by reduced serum lipopolysaccharide level, and increased ileum expression of tight junction proteins and antimicrobial peptides. Fecal microbiota transplantation study confirmed that BSGLP-induced microbiota change is responsible, at least in part, for obesity inhibition. Besides, BSGLP notably alleviated HFD-induced upregulation of TLR4/Myd88/NF-κB signaling pathway in adipose tissue. Collectively, our study showed for the first time that BSGLP might be used as a prebiotic agent to inhibit obesity and hyperlipidemia through modulating inflammation, gut microbiota, and gut barrier function.

The interaction between gut microbiota and flavonoid extract from Smilax glabra Roxb. and its potent alleviation of fatty liver.

Fatty liver is associated with intestinal microbiota dysbiosis and low-grade chronic inflammation. Herein we report the interaction of the flavonoid extract from Smilax glabra Roxb. (FSGR) with gut microbiota. Then, FSGR's function of modulating microbiota in a rat model of high-fat diet (HFD) induced fatty liver has been explored. These investigations indicated that the main compound in FSGR, such as astilbin and its isomers, could be metabolized to aglycone, while further splitting resulted in some phenolic acid compounds through a redox reaction. The data obtained clearly showed that FSGR not only alleviated the steatosis degree of liver cells and modulated the contents of short chain fatty acids (SCFAs) in the intestinal tract, but also reversed gut dysbiosis induced by HFD as prognosticated by the decreased ratio of Firmicutes/Bacteroidetes (F/B) and altered gene expression. The results demonstrated that FSGR probably could be used as a prebiotic agent to impede gut dysbiosis and fatty liver-related metabolic disorders.

Sulfated polysaccharides from Undaria pinnatifida improved high fat diet-induced metabolic syndrome, gut microbiota dysbiosis and inflammation in BALB/c mice

Undaria pinnatifida was shown to reduce serum lipids and fat accumulation and produce beneficial effect on type 2 diabetes, but its effect on intestinal micro-ecology remains unclear. This study showed that sulfated polysaccharides from U. pinnatifida (UPSP) reduced weight gain, fat accumulation and metabolic disorders in mice fed with high fat diet (HFD). UPSP not only alleviated HFD-induced microbiota dysbiosis indicated as increased abundances of some Bacteroidales members that had positive correlations with the improvement of physiological indexes, but also maintained gut barrier integrity and reduced metabolic endotoxemia. A dose-effect relationship was observed between the dose of UPSP and its effect on some physiological indexes, gut microbiota community and nutrient utilization. The in vitro result showed that the use of Bacteroides species within Bacteroidales on UPSP was species-dependent, and the dose of UPSP affected the growth properties of some Bacteroides species. It implied that UPSP can be considered as prebiotic agent to prevent gut dysbiosis and obesity-related diseases in obese individuals.

Nutritional Therapies for Irritable Bowel Syndrome: a Focus on Prebiotics and Probiotics

The pathophysiology of irritable bowel syndrome (IBS) is incompletely understood, but in at least some patients, alterations in the gut microbiome are likely to be etiologically relevant. The purpose of this review is to evaluate the available evidence to date for the use of prebiotics and probiotics in the treatment of IBS, with particular attention to broad themes in therapeutic rationale as well as critical gaps in the literature. A number of individual studies and meta-analyses have demonstrated efficacy in the use of prebiotics and probiotics for IBS. Even so, variability in study design, risk of bias, and short follow-up intervals limit the ability to draw robust conclusions in aggregate. More research is needed to understand the intricacy of the gut microbiome and how it relates to IBS symptomatology, but the effectiveness of prebiotic and probiotic agents demonstrated so far implies a worthy therapeutic signal within the noise.

Stachyose Improves the Effects of Berberine on Glucose Metabolism by Regulating Intestinal Microbiota and Short-Chain Fatty Acids in Spontaneous Type 2 Diabetic KKAy Mice.

Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using KKAy mice. Here, we find that the combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combined administration enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR. Additionally, BBR with Sta significantly reduces the concentrations of fecal short-chain fatty acids compared to BBR. Collectively, these results indicate that the combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and short-chain fatty acids, thereby providing a novel approach for the treatment of type 2 diabetes mellitus.

Prebiotic effects of olive pomace powders in the gut: In vitro evaluation of the inhibition of adhesion of pathogens, prebiotic and antioxidant effects

Olive pomace is a biowaste rich in polyphenols and insoluble dietary fibre with high potential to develop new value chains towards a sustainable and circular bioeconomy. Regarding gut health, olive pomace phenolics and insoluble dietary fibre (after possible fermentation) could act as antioxidants, antimicrobial and prebiotic agents. These potential beneficial effects on the gut were analysed for two powders from olive pomace: liquid-enriched powder (LOPP) - mostly source of phenolics - and pulp-enriched powder (POPP) - main source of insoluble dietary fibre. LOPP and POPP were subjected to an in vitro simulated gastrointestinal digestion followed by in vitro faecal fermentation. The undigested fraction retained in the colon was analysed regarding its potential antioxidant, antimicrobial and prebiotic effects. LOPP and POPP did not impact the gut microbiota diversity negatively, showing a similar ratio of Firmicutes/Bacteroidetes compared to a positive control (FOS). LOPP exhibit a positive (similar to FOS) effect on the Prevotella spp./Bacteroides spp. ratio. Both powders promoted more the production of short-chain fatty acids (mainly acetate > butyrate > propionate) than FOS and showed also significant total phenolic content and oxygen radical absorbance capacity during faecal fermentation until 48 h. Besides that, these powders showed mucin-adhesion inhibition ability against pathogens, principally POPP against Bacillus cereus (22.03 ± 2.45%) and Listeria monocytogenes (20.01 ± 1.93%). This study demonstrates that olive pomace powders have prebiotic effects on microbiota, including the stimulation of short-chain fatty acids production, potential antioxidant and antimicrobial activity which could improve the human gut health.

Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice.

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.

Green Tea Encourages Growth ofAkkermansia muciniphila

Trillions of microorganisms reside in the hosts' gut. Since diverse activities of gut microbiota affect the hosts' health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.

Dendrobium officinale Kimura et Migo and American ginseng mixture: A Chinese herbal formulation for gut microbiota modulation.

Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.

Ameliorative Effect of Gum Acacia on Hookah Smoke-Induced Testicular Impairment in Mice.

We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The urinary level of cotinine, a major nicotine metabolite, was also measured. HS exposure induced significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein, as well as glutathione reductase activity and levels of nitrite and total nitrite. Plasma inhibin B, alkaline phosphatase, lipopolysaccharide binding protein, uric acid, lactate dehydrogenase, lipid peroxidation, 8-oxo-2’-deoxyguanosine, and cytochrome C were significantly increased following HS exposure. In testicular homogenate, nuclear factor-κB (NF-ĸB), nuclear factor erythroid 2–related factor 2 (Nrf2), interleukin- 6 (IL-6), interleukin-1β (IL-1β), transforming growth factor-β1(TGF- β1), and tumor necrosis factor-α (TNF- α) were all significantly elevated, and the steroidogenic acute regulatory protein (StAR) significantly decreased. Histopathologically, there was slight impairment and disorganization of spermatogenesis. Urinary cotinine concentration was elevated significantly in the HS-exposed group compared with the air-exposed group. GA co-administration mitigated the adverse actions of HS measured. In conclusion, daily exposure to HS at the above dose induced adverse actions on the reproductive system of male mice. GA co-administration significantly mitigated these effects by reducing the inflammation, oxidative and nitrosative stress, via a mechanism involving Nrf2, and reduction of StAR expression.

Protective effect of baicalin on the regulation of Treg/Th17 balance, gut microbiota and short-chain fatty acids in rats with ulcerative colitis.

Baicalin is reported as an effective drug for ulcerative colitis (UC). However, its effect on gut microbiota and short-chain fatty acids (SCFAs) remains unknown. In this study, we investigated the role of baicalin on Th17/Treg balance, gut microbiota community, and SCFAs levels in trinitrobenzene sulphonic acid (TNBS)-induced UC rat model. We found the DAI scores were significantly increased in the TNBS-treated rats, while reduced in the baicalin-treated group in a dose-dependent manner, accompanied with the alleviation of mucosal injury, the reduction of ZO-1, Occludin, and MUC2 expression. At the meanwhile, baicalin repressed the increased levels of reactive oxygen species (ROS) and MDA, while deceased the GSH and SOD levels in colon tissue of rats treated with TNBS. On the other hand, administration of baicalin attenuated the TNBS-induced upregulations of Th17/Treg ratio, indicating a strong amelioration in the colorectal inflammation. More importantly, pyrosequencing of the V4 regions of 16S rRNA genes in rat feces revealed a deviation of the gut microbiota in response to baicalin treatment. In particular, the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that baicalin reversed TNBS-induced gut dysbiosis OTUs. In addition, we further investigated the fecal levels of major SCFAs in rats and found that baicalin significantly resorted the fecal butyrate levels in rats treated with TNBS. The increased butyrate levels were in consistent with the higher abundance of butyrate-producing species such as Butyricimonas spp., Roseburia spp., Subdoligranulum spp., and Eubacteriu spp. in baicalin-treated group. In conclusion, our findings suggest that baicalin possibly protected rats against ulcerative colitis by regulation of Th17/Treg balance, and modulation of both gut microbiota and SCFAs. Baicalin may be used as a prebiotic agent to treat ulcerative colitis-associated inflammation and gut dysbiosis.

Plant-polyphenols based second-generation synbiotics: Emerging concepts, challenges, and opportunities.

There is a growing interest in identifying alternatives to traditional oligosaccharide-based prebiotic agents owing to their undesirable attributes, such as a lack of microbial growth specificity and limited inherent bioactivity. In addition, a novel concept of second-generation synbiotic agents is currently emerging, which argues that prebiotic agents could be best defined on the basis of their physiological effects or functional capacities in the host rather than their specific microbial targets. Plant polyphenols are rapidly emerging as suitable prebiotic and synbiotic candidates that may fulfil these criteria. As we begin to understand the intricate interrelationship between dietary polyphenols and the gut microbiome, a functional synergy can be observed that suggests the appropriateness of the amalgamation of polyphenols and probiotic agents to develop second-generation synbiotic agents. In the present review, we study evidence pertaining to the prebiotic and synbiotic attributes of polyphenols, as well as their relationship with probiotic bacteria, and discuss their efficacy, suitability, and strategies to develop second-generation synbiotic agents. We provide a perspective that polyphenol-based synbiotic agents are fundamentally superior to the traditional carbohydrate-based synbiotic agents and could therefore offer health benefits of both polyphenols and probiotic agents in a synergistic manner.

Tuna Bone Powder Alleviates Glucocorticoid-Induced Osteoporosis via Coregulation of the NF-κB and Wnt/β-Catenin Signaling Pathways and Modulation of Gut Microbiota Composition and Metabolism.

The effects and mechanism of tuna bone powder (TBP) on glucocorticoid-induced osteoporosis (GIOP) alleviation in terms of signaling pathway coregulation and gut microbiota modulation are investigated. The powder size distribution and composition of TBP are measured. The GIOP female mice induced by dexamethasone intramuscular injection are used to examine the anti-osteoporosis effects of TBP in a 10 week experiment, and improved bone mineral density and bone microarchitecture are observed via micro-CT. In addition, qRT-PCR results show that the NF-κB pathway is inhibited to reduce bone resorption, whereas the Wnt/β-catenin pathway is activated to enhance bone formation after treatment. Moreover, TBP treatments suppress the release of pro-inflammatory cytokines, repair dysfunction of the intestinal epithelial barrier, and prevent aggravated systemic inflammation in mRNA levels. Additionally, 16S rRNA gene sequencing indicate that TBP treatments enhance the abundance of anti-inflammatory bacteria and short-chain fatty acid (SCFA) producers, which is consistent with increased SCFA contents in feces measured via GC-MS. These data show that TBP ameliorates GIOP in mice through four aspects, including coregulating signaling pathways, blocking proinflammatory cytokines, repairing the intestinal epithelial barrier, and modulating gut microbiota. Therefore, TBP may be a potential prebiotic agent to alleviate osteoporosis in humans.