SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.

Adverse intestinal microbiome profiles described as a dysbiotic gut are a complicit etiological operative factor that can progress and maintain inflammatory sequelae in the intestines. The disruption of the gut microbiome that ensues with intestinal dysbiosis is, for example, posited by decreases in the alpha-diversity of the gut microbiome, which is characterized by significant reductions in the abundance of bacterial members from the Bacteroidetes and Firmicutes phyla. Proteobacteria have often been recognized as gut microbial signatures of disease. For example, this happens with observed increases in abundance of the phyla Proteobacteria and Gammaproteobacteria, such as the adherent-invasive Escherichia coli strain, which has been significantly linked with maintaining inflammatory bowel diseases. Research on the administration of probiotics, often identified as gut-functional foods, has demonstrated safety, tolerability, and efficacy issues in treating inflammatory bowel diseases (IBDs). In this narrative review, we explore the efficacy of probiotics in treating IBDs with bacterial strain- and dose-specific characteristics and the association with multi-strain administration.

In this study, the utilization mechanism of oligosaccharides by Bifidobacterium was investigated through the transcriptome sequencing and non-targeted metabolomics technology of Bifidobacterium animalis cultured with fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS). The results showed that FOS affected the synthesis of adenosine triphosphate binding transporters (ABC transporters) by increasing the expression levels of msmE, msmG, and gluA. Similarly, GOS improved aminoacyl-tRNA synthases by upregulating the expression of tRNA-Ala, tRNA-Pro, and tRNA-Met. Bifidobacterium animalis cultured with FOS and GOS produced different metabolites, such as histamine, tartaric acid, and norepinephrine, with the functions of inhibiting inflammation, alleviating depression and diseases related to brain and nervous system and maintaining body health. Furthermore, the transcriptome and metabolome analysis results revealed that FOS and GOS promoted the growth and metabolism of Bifidobacterium animalis by regulating the related pathways of carbohydrate, energy, and amino acid metabolism. Overall, the experimental results provided significant insights into the prebiotic effects of FOS and GOS.

Citrus peels contain abundant polyphenols, particularly flavonoids, and have been shown to exert lipid accumulation decreasing ability. In this study, Citrus depressa peel applied to oven drying and extracted with ethanol extract as CDEE to analyze its flavonoids compositions and investigated its effects on a high-fat diet (HFD)-induced obese mice model. CDEE contained several flavonoids such as hesperidin, sinesentin, nobiletin, tangeretin, 5-demethylnobiletin, and 5-demethyltangeretin. The mice fed an HFD, and administration of 2% CDEE to could decrease weight gain, abdominal fat weight, inguinal fat weight, and the adipocyte size, and CDEE also reduced serum total cholesterol (TCHO), triacylglycerol (TG) compared with mice fed only on HFD. CDEE hindered lipid accumulation through a decreased fatty acid synthase (FAS) protein expression via upregulation of the protein expression of AMP-activated protein kinase α (AMPKα). Moreover, CDEE modulated gut microbiota that altered by HFD through an increased abundance of Lactobacillus reuteri compared with the HFD group. The results demonstrated that CDEE helps decrease lipid accumulation through the AMPK pathway, which also indicates a prebiotic-like effect on gut microbiota.

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Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as Bifidobacterium associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut Bifidobacterium, as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.

Carbohydrates have a dietary role, but excessive consumption of high-calorie sugars can contribute to an increased incidence of metabolic diseases and dental caries. Recently, carbohydrates with sweetening properties and low caloric value, such as D-tagatose, have been investigated as alternative sugars. D-tagatose is a rare sugar that has nutritional and functional properties of great interest for health. This literature review presents an approach to the biological effects of D-tagatose, emphasizing its benefits for oral health. Studies report that D-tagatose has antioxidant and prebiotic effects, low digestibility, reduced glycemic and insulinemic responses, and the potential to improve the lipid profile, constituting an alternative for diabetes mellitus and obesity. It can also be observed that D-tagatose has an antioxidant action, favoring the elimination of free radicals and, consequently, causing a reduction in cellular oxidative stress. Furthermore, it also has antibacterial potential against oral species. Regarding oral health, studies have shown that D-tagatose efficiently reversed bacterial coaggregations, including periodontopathogenic species, and impaired the activity and growth of cariogenic bacteria, such as S. mutans. D-tagatose significantly inhibited biofilm formation, pH decrease and insoluble glucan synthesis in S. mutans cultures. Salivary S. mutans counts were also significantly reduced by the consumption of chewing gum containing D-tagatose and xylitol. In addition, there is evidence that tagatose is effective as an air-polishing powder for biofilm decontamination. The literature indicates that D-tagatose can contribute to the prevention of systemic diseases, also constituting a promising agent to improve oral health.

Type 2 diabetes is a disease with significant health consequences for the individual. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. One of them is the association of type 2 diabetes with microbiota. Through the enteric nervous system and the gut-microbiota axis, the microbiota affects the functioning of the body. It has been proven to have a real impact on influencing glucose and lipid metabolism and insulin sensitivity. With dysbiosis, there is increased bacterial translocation through the disrupted intestinal barrier and increased inflammation in the body. In diabetes, the microbiota\'s composition is altered with, for example, a more abundant class of Betaproteobacteria. The consequences of these disorders are linked to mechanisms involving short-chain fatty acids, branched-chain amino acids, and bacterial lipopolysaccharide, among others. Interventions focusing on the gut microbiota are gaining traction as a promising approach to diabetes management. Studies are currently being conducted on the effects of the supply of probiotics and prebiotics, as well as fecal microbiota transplantation, on the course of diabetes. Further research will allow us to fully develop our knowledge on the subject and possibly best treat and prevent type 2 diabetes.

Iron deficiency remains a public health challenge globally. Prebiotics have the potential to improve iron bioavailability by modulating intestinal bacterial population, increasing SCFA production, and stimulating expression of brush border membrane (BBM) iron transport proteins among iron-deficient populations. This study intended to investigate the potential effects of soluble extracts from the cotyledon and seed coat of three pea (Pisum sativum) varieties (CDC Striker, CDC Dakota, and CDC Meadow) on the expression of BBM iron-related proteins (DCYTB and DMT1) and populations of beneficial intestinal bacteria in vivo using the Gallus gallus model by oral gavage (one day old chicks) with 1 mL of 50 mg/mL pea soluble extract solutions. The seed coat treatment groups increased the relative abundance of Bifidobacterium compared to the cotyledon treatment groups, with CDC Dakota seed coat (dark brown pigmented) recording the highest relative abundance of Bifidobacterium. In contrast, CDC Striker Cotyledon (dark-green-pigmented) significantly increased the relative abundance of Lactobacillus (p < 0.05). Subsequently, the two dark-pigmented treatment groups (CDC Striker Cotyledon and CDC Dakota seed coats) recorded the highest expression of DCYTB. Our study suggests that soluble extracts from the pea seed coat and dark-pigmented pea cotyledon may improve iron bioavailability by affecting intestinal bacterial populations.

With the aim to obtain controlled-release systems and to preserve the antioxidant, immunomodulatory, and prebiotic activity of the bioactive compounds, microencapsulation of both honeydew honey and royal jelly into biopolymeric microparticles based on rye bran heteropolysaccharides (HPS) was successfully performed. Honeydew honey and royal jelly microcapsules were prepared by spray-drying method and were characterized in terms of morphology and biological properties. Due to the resistance of the obtained encapsulates to the acidic pH in the stomach and digestive enzymes, the microcapsules showed prebiotic properties positively influencing both the growth, retardation of the dying phase, and the pro-adhesive properties of probiotic bacteria, i.e., Bifidobacterium spp. and lactic acid bacteria. Moreover, as a result of fermentation of the microcapsules of bee products in the lumen of the large intestine, an increased synthesis of short-chain fatty acids, i.e., butyric acid, was found on average by 39.2% in relation to the SCFA concentrations obtained as a result of fermentation of native bee products, thus opening new perspectives for the exploitation of honeydew honey and royal jelly loaded microcapsules for nutraceutical applications.