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•The missing point in the current study of functional foods and gut microbiota is discussed.•Methods for establishing causation in the study of functional foods and gut microbiota are ...summarized.•Future study in the field of functional foods and gut microbiota should move from correlation to causation.
Recently, there has been an unprecedented interest in the study of gut microbiota during treatment of diseases by functional foods. However, although great progresses have been made, a significant knowledge gap still exists. The knowledge gap, as argued here, is that in most of the studies we failed to establish a cause–effect relationship between attenuation of the diseases and changes of the gut microbiota. The lack of causation studies deteriorates the foundation for the use of functional foods in disease management that aim to target the gut microbiota. In this sense, we propose here that future studies on the interactions of functional foods and gut microbiota during the treatment of diseases must move beyond correlation to causation, and only after a cause–effect relationship has been established can we fully realize the therapeutic potential of functional foods in the upcoming era of microbiota targeted precision nutrition.
•Fucoidan reduces systematic inflammation and attenuates MetS in HFD-fed mice.•Fucoidan increases Akkermansia population in the gut microbiota of mice with MetS.•Fucoidan ameliorates MetS in ...association with a robust modulation of gut microbiota.
Emerging evidence shows that dietary fucoidan contribute to the prevention and treatment of diverse diseases. Here, using a mouse model, we first demonstrate a similar beneficial effect of two fucoidans from Laminaria japonica and Ascophyllum nodosum on diet-induced metabolic syndrome (MetS). Both fucoidans were found to significantly reduce body weight, fasting blood glucose, hepatic steatosis and systematic inflammation. To decipher the mechanism behind this therapeutic effect, the gut microbiota was analyzed as fucoidan is poorly absorbed after oral administration. Interestingly, we found that benign microbes which conferred benefits upon host wellbeing including Akkermansia muciniphila and short-chain fatty acid-producers such as Alloprevotella, Blautia and Bacteroides were highly enriched by fucoidans. Collectively, our study illustrates a novel application of fucoidan as an anti-MetS functional food and, from a gut microbiota perspective, sheds new insight into the mechanism by which unabsorbed polysaccharide exerts a system therapeutic effect.
Oral preparations of chondroitin sulfate (CS) have long been used as anti-osteoarthritis (anti-OA) drugs. However, little is known about the degradation of CS by human gut microbiota. In the present ...study, degradation profiles of CSA (the main constituent of CS drugs) by the human gut microbiota from six healthy subjects were investigated. Each individual’s microbiota had differing degradation activities, but ΔUA-GalNAc4S was the end product in all cases. To elucidate the mechanisms underlying this phenomenon, different CSA-degrading bacteria were isolated from each individual’s microbiota and tested for CSA degradation. In addition to Bacteroides thetaiotaomicron J1, Bacteroides thetaiotaomicron 82 and Bacteroides ovatus E3, a new CSA-degrading bacterium, Clostridium hathewayi R4, was isolated and characterized. Interestingly, at least two different CSA-degrading species were identified from each individual’s gut microbiota. Predictably, these functional bacteria also had differing degradation rates, but still generated the same end product, ΔUA-GalNAc4S. In addition, the human fecal isolates produced different degradation profiles for CSC, CSD, and CSE, suggesting that CS could be readily metabolized to varying extents by diverse microbial consortiums, which may help to explain the poor bioavailability and unequal efficacy of CS among individuals in OA treatment.
Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate the anti-colitis effect of ...alginate has not been fully characterized. We hypothesized that alginate-degrading bacteria might play a role here since these bacteria could utilize alginate as a carbon source. To test this hypothesis, we isolated 296 strains of alginate-degrading bacteria from the human gut.
AY11-1 was observed to have the best capability for alginate degradation. The degradation and fermentation of alginate by
AY11-1 produced significant amounts of oligosaccharides and short-chain fatty acids. Further studies indicated that
AY11-1 could alleviate body weight loss and contraction of colon length, reduce the incidences of bleeding and attenuate mucosal damage in dextran sulfate sodium (DSS)-fed mice. Mechanistically,
AY11-1 improved gut dysbiosis and promoted the growth of probiotic bacteria, including
spp. And
, in diseased mice. Additionally,
AY11-1 showed no oral toxicity and was well-tolerated in male and female mice. Altogether, we illustrate for the first time an anti-colitis effect of the alginate-degrading bacterium
AY11-1. Our study paves the way for the development of
AY11-1 as a next-generation probiotic bacterium.
Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after ...oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.
Recently, accumulating evidence has suggested that
polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has ...been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of
spp. and
, a next-generation probiotic bacterium, whereas in males, ECP increased the population of
spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.
Polysaccharide from the edible alga
has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, ...using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that
polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of
spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of
F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally,
F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria
.
De novo lipogenesis is tightly regulated by insulin and nutritional signals to maintain metabolic homeostasis. Excessive lipogenesis induces lipotoxicity, leading to nonalcoholic fatty liver disease ...(NAFLD) and type 2 diabetes. Genetic lipogenic programs have been extensively investigated, but epigenetic regulation of lipogenesis is poorly understood. Here, we identified Slug as an important epigenetic regulator of lipogenesis. Hepatic Slug levels were markedly upregulated in mice by either feeding or insulin treatment. In primary hepatocytes, insulin stimulation increased Slug expression, stability, and interactions with epigenetic enzyme lysine-specific demethylase-1 (Lsd1). Slug bound to the fatty acid synthase (Fasn) promoter where Slug-associated Lsd1 catalyzed H3K9 demethylation, thereby stimulating Fasn expression and lipogenesis. Ablation of Slug blunted insulin-stimulated lipogenesis. Conversely, overexpression of Slug, but not a Lsd1 binding-defective Slug mutant, stimulated Fasn expression and lipogenesis. Lsd1 inhibitor treatment also blocked Slug-stimulated lipogenesis. Remarkably, hepatocyte-specific deletion of Slug inhibited the hepatic lipogenic program and protected against obesity-associated NAFLD, insulin resistance, and glucose intolerance in mice. Conversely, liver-restricted overexpression of Slug, but not the Lsd1 binding-defective Slug mutant, had the opposite effects. These results unveil an insulin/Slug/Lsd1/H3K9 demethylation lipogenic pathway that promotes NAFLD and type 2 diabetes.
Previous studies have demonstrated that the intestinal abundance of Bacteroides uniformis is significantly higher in healthy controls than that in patients with ulcerative colitis (UC). However, what ...effect B. uniformis has on the development of UC has not been characterized. Here, we show for the first time that B. uniformis F18-22, an alginate-fermenting bacterium isolated from the healthy human colon, protects against dextran-sulfate-sodium (DSS)-induced UC in mice. Specifically, oral intake of B. uniformis F18-22 alleviated colon contraction, improved intestinal bleeding and attenuated mucosal damage in diseased mice. Additionally, B. uniformis F18-22 improved gut dysbiosis in UC mice by increasing the abundance of anti-inflammatory acetate-producing bacterium Eubacterium siraeum and decreasing the amount of pro-inflammatory pathogenetic bacteria Escherichia-Shigella spp. Moreover, B. uniformis F18-22 was well-tolerated in mice and showed no oral toxicity after repeated daily administration for 28 consecutive days. Taken together, our study illustrates that B. uniformis F18-22 is a safe and novel probiotic bacterium for the treatment of UC from the healthy human colon.
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