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D-Tagatose is partly absorbed in the stomach and small intestine. Most of it is fermented by the large intestinal microbiota. The effect of D-tagatose on the composition of the microbiota and production of short chain fatty acids (SCFAs) was studied in vivo and in vitro. Gastrointestinal (GI) complaints were also studied. The in vivo study was performed according to a randomized, placebo-controlled, double-blind, five-way cross-over design in healthy subjects (12 men and 18 women). All subjects consumed 30 g raspberry jam containing 7.5 or 12.5 g D-tagatose, 7.8 g fructo-oligosaccharides (positive reference), 7.6 g D-tagatose plus 7.5 g fructo-oligosaccharides, or 15.1 g sucrose (negative reference) at breakfast for 2 weeks in different orders. At the end of each treatment period lipids and safety parameters in blood and GI complaints were evaluated by questionnaires, and faecal microbiota and SCFAs were measured. Furthermore, test-tube incubations of faecal slurries with D-tagatose, fructo-oligosaccharides and sucrose were performed. An in vitro model simulating the large intestine was used to assess the mechanistic effect of D-tagatose on microbiota composition and SCFA production. The high-tagatose treatment resulted in increased numbers of faecal lactobacilli in men, but not in women. Also in vitro, lactobacilli increased. Both the test-tube incubations of fresh faeces from the in vivo study with D-tagatose and the study in the in vitro model showed increased butyrate production after all treatments with D-tagatose. High-tagatose, but not low-tagatose, resulted in a slightly increased defecation frequency and stools of thinner consistency. Only a few GI complaints were reported. The data indicate that daily consumption of 7.5 or 12.5 g D-tagatose may lead to increased production of butyrate and to an increase of lactobacilli, without serious GI complaints. In view of the health-promoting effects of butyrate and lactobacilli, D-tagatose may be considered a prebiotic substrate.

D-tagatose, a monosaccharide as well as a dietary supplement, has been reported as having a wide range of applicability in the food industry, however, the prebiotic activity, anticonstipation effects, and related mechanisms are still unclear. In this study, using the loperamide-induced constipation Kunming mice as the animal model, the effects of d-tagatose for the prevention of constipation were evaluated by gastrointestinal transit experiment and defecation experiment. Furthermore, the underlying mechanism was clarified by evaluating the change of the biochemical indicators and analyzing 16S rRNA amplicon of gut microbiota among the different mice groups. The results showed that the gastrointestinal transit rate, fecal number, and weight in six hours were significantly enhanced after the administration of d-tagatose. In addition, d-tagatose significantly increased the serum levels of acetylcholine (Ach) and substance P (SP), whereas the serum levels of nitric oxide (NO) were significantly decreased. Moreover, the 16S rRNA sequencing analysis revealed that the changes in the gut microbiota caused by constipation were restored by d-tagatose treatment. In conclusion, this study indicated that the administration of d-tagatose as a dietary supplement can effectively prevent and relieve constipation in Kunming mice, and it is a promising prebiotic candidate with constipation-relieving properties.

Knowledge of the fermentation pattern of D-tagatose is important for the assessment of energy value and compliance of D-tagatose. In vitro fermentation experiments with pig intestinal contents and bacteria harvested from the gastrointestinal tract of pigs were used to investigate the degradation of D-tagatose and the formation of fermentation products. Two groups of eight pigs were fed either a control diet containing 150 g/kg sucrose or a diet which had 100 g/kg of the sucrose replaced by D-tagatose. After 18 d the pigs were killed and the gastrointestinal contents collected for in vitro studies. No microbial fermentation of D-tagatose occurred in the stomach or in the small intestine, whereas the sugar was fermented in the cecum and colon. Formate, acetate, propionate, butyrate, valerate, caproate and some heptanoate were produced by the microbial fermentation of D-tagatose by gut microbiota. Hydrogen and methane were also produced. The population of D-tagatose-degrading bacteria in fecal samples and the capacity of bacteria from the hindgut to degrade D-tagatose were higher in the pigs adapted to D-tagatose compared with unadapted pigs. In unadapted pigs, the major fermentation product from D-tagatose was acetic acid. Much more butyric and valeric acids were produced from D-tagatose by bacterial slurries of tagatose-adapted pigs compared with unadapted pigs; this was especially the case for samples from the colon. We conclude that D-tagatose is not fermented in the upper gastrointestinal tract, and the ability of the large intestinal microbiota to ferment D-tagatose is dependent on adaptation.

The digestibility of D-tagatose, its effect on the digestibility of macronutrients and the metabolic response of the microbiota of the gastrointestinal tract to the ingestion of this carbohydrate were studied in pigs. Eight pigs were fed a low fiber diet comprising 15% sucrose (control group). Another eight pigs were fed a similar diet except that 100 g sucrose per kg diet was replaced by D-tagatose (test group). After 18 d, the pigs were killed and the gastrointestinal contents removed for analysis. The digestibility of D-tagatose was 25.8 +/- 5.6% in the distal third of the small intestine. The small intestinal digestibilities of dry matter (86.9 +/- 1.3 vs. 92.9 +/- 0.9%), gross energy (74.4 +/- 1.6 vs. 80.7 +/- 1.8%) and sucrose (90.4 +/- 2.5 vs. 98.0 +/- 0.5%) were lower (P < 0. 05) in the pigs fed D-tagatose. Digestibilities of starch, protein and fat did not differ between groups. D-Tagatose, sucrose and starch were fully digested in the large intestine. The fecal digestibilities of energy, dry matter and fat did not differ between the two groups, whereas D-tagatose reduced the fecal digestibility of protein (91.1 +/- 0.6 vs. 93.5 +/- 0.7%, P < 0.05). D-Tagatose served as a substrate for the microbiota in the cecum and proximal colon as indicated by a reduced pH, and a greater ATP concentration, adenylate energy charge (AEC) ratio and concentration of short-chain fatty acids. In particular, the increase in the concentrations of propionate, butyrate and valerate suggests possible health benefits of this monosaccharide.

A number of 174 normal or pathogenic human enteric bacteria and dairy lactic acid bacteria were screened for D-tagatose fermentation by incubation for 48 hours. Selection criteria for fermentation employed included a drop in pH below 5.5 and a distance to controls of more than 0.5. Only a few of the normal occurring enteric human bacteria were able to ferment D-tagatose, among those Enterococcus faecalis, Enterococcus faecium and Lactobacillus strains. D-Tagatose fermentation seems to be common among lactic acid bacteria. Most of the analyzed dairy lactic acid bacteria fermented D-tagatose, and among those Lactobacillus, Leuconostoc and Pediococcus strains fermented most strongly, but also strains of Enterococcus, Streptococcus and Lactococcus fermented D-tagatose. None of the analyzed Bifidobacterium strains fermented tagatose.

Healthy adult women were administered D-tagatose (TAG) and the maximum no-effect dose for transient diarrhea was determined. Next, the effects of TAG ingestion on blood glucose and insulin levels, blood TAG concentration and urinary excretion, and exhaled hydrogen gas after TAG ingestion were measured, and the fate of D-tagatose in the body was examined by observing its digestibility and absorption from the small intestine, its fermentation in the large intestine, and its assimilation by intestinal bacteria. The maximum no-effect dose of TAG was 0.25 g/kg body weight, which was similar to that of D-sorbitol. When 5 g and 10 g of TAG were administered, the blood TAG concentration was below the detection limit. Furthermore, the urinary excretion up to 6 hours after ingestion was less than 2% of the amount ingested. Blood glucose and serum insulin concentrations were not changed by TAG ingestion, and exhaled hydrogen gas excretion was not observed with 5 g of TAG, but was clearly increased with 10 g of TAG. However, the amount was smaller than that of the same amount of fructooligosaccharides, and the onset of excretion was delayed. Furthermore, the amount of organic acids produced from TAG in human feces culture experiments was small, suggesting that TAG reaching the large intestine was metabolized to a small amount of short-chain fatty acids by intestinal bacteria. From these results, it was estimated that ingestion of 10 g of TAG did not induce diarrhea, about 5 g was absorbed from the small intestine, and about 2% of the ingested amount was excreted in the urine without being metabolized. The available energy of TAG was estimated based on these results, and the energy conversion coefficient of TAG was classified as 2 kcal/g.

In the current study, we have tested the nonenzymatic glycation activities of ketohexoses, such as tagatose and psicose. Although tagatose-treated apoA-I (t-A-I) and psicose-treated apoA-I (p-A-I) exerted more inhibitory activity you cupric ion-mediated low-density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL) phagocytosis into macrophage than fructose-treated apoA-I (f-A-I). In the lipid-free state, t-A-I and f-A-I showed more multimerized band without crosslinking. Since t-A-I lost its phospholipid binding ability, the rHDL formation was not as successful as f-A-I. However, injecting t-A-I showed more antioxidant activities in zebrafish embryo under the presence of oxLDL. Three weeks of consumption of fructose (50% of wt in Tetrabit/4% cholesterol) showed a 14% elevation of serum triacylglycerol (TG), while tagatose-administered group showed 30% reduction in serum TG compared to high cholesterol control. Fructose-fed group showed the biggest area of Oil Red O staining with the intensity as strong as the HCD control. However, tagatose-consumed group showed much lesser Oil Red O-stained area with the reduction of lipid accumulation. In conclusion, although tagatose treatment caused modification of apoA-I, the functional loss was not as much severe as the fructose treatment in macrophage cell model, zebrafish embryo, and hypercholesterolemic zebrafish model.

The hepatic glucose fasting response is gaining traction as a therapeutic pathway to enhance hepatic and whole-host metabolism. However, the mechanisms underlying these metabolic effects remain unclear. Here, we demonstrate the epidermal-type lipoxygenase, eLOX3 (encoded by its gene, Aloxe3), is a potentially novel effector of the therapeutic fasting response. We show that Aloxe3 is activated during fasting, glucose withdrawal, or trehalose/trehalose analogue treatment. Hepatocyte-specific Aloxe3 expression reduced weight gain and hepatic steatosis in diet-induced and genetically obese (db/db) mouse models. Aloxe3 expression, moreover, enhanced basal thermogenesis and abrogated insulin resistance in db/db diabetic mice. Targeted metabolomics demonstrated accumulation of the PPARγ ligand 12-KETE in hepatocytes overexpressing Aloxe3. Strikingly, PPARγ inhibition reversed hepatic Aloxe3–mediated insulin sensitization, suppression of hepatocellular ATP production and oxygen consumption, and gene induction of PPARγ coactivator-1α (PGC1α) expression. Moreover, hepatocyte-specific PPARγ deletion reversed the therapeutic effect of hepatic Aloxe3 expression on diet-induced insulin intolerance. Aloxe3 is, therefore, a potentially novel effector of the hepatocellular fasting response that leverages both PPARγ-mediated and pleiotropic effects to augment hepatic and whole-host metabolism, and it is, thus, a promising target to ameliorate metabolic disease.

Trehalose and its analogues are promising cardiometabolic therapeutic agents with pleiotropic effects across tissue types. It is likely that we are only beginning to uncover the broad efficacy and complex mechanisms by which these compounds modulate host metabolism.

Tagatose, a low-calorie natural sugar, has recently received FDA GRAS status, allowing its use as a sweetener in food and beverages. This paper provides an overview of tagatose, including its applications in food and beverages and potential health benefits. Safety studies conducted according to FDA guidelines support its GRAS status. Small clinical trials have shown tagatose to be effective in treating type 2 diabetes. It is a safe and effective low-calorie sweetener for various products, particularly those that require bulk, such as chocolates, gum, cakes, and ice cream. Tagatose can also complement high-intensity sweeteners in sodas. Additionally, it has potential health benefits, including treating diabetes, hyperglycemia, anemia, hemophilia, and supporting fetal development.

This study aimed to compare the temporal sweetness and qualitative differences of 15 sweeteners to sucrose. Various sweeteners from different groups were evaluated by 20 participants using the Temporal Check-all-that-Apply (TCATA) method. Sucrose exhibited a rapid onset of sweetness and minimal side tastes. Acesulfame-K, stevia, and luo han guo had prominent bitter, metallic, and chemical tastes. Allulose, erythritol, sorbitol, aspartame, and sucralose had some side tastes but maintained sweetness. Nutritive sweeteners like dextrose, fructose, maltitol, mannitol, sucrose-allulose mixture, palatinose, and xylitol had taste profiles most similar to sucrose in terms of sweetness onset, peak sweetness, decay, and side tastes. This information can help in selecting suitable sucrose substitutes based on taste profiles.

This study compared the taste properties of different sweeteners in three food matrices (black tea, chocolate milk, and natural yogurt) to sucrose. The sensory properties of each sweetener varied across the matrices, with some sweeteners closely resembling sucrose taste in all foods. Others had distinct taste profiles characterized by side tastes and lower sweetness. Sweeteners performed differently in natural yogurt compared to tea and chocolate milk. These findings emphasize the need to consider complex food matrices when selecting sweeteners as sugar substitutes. Food manufacturers can use these results to identify suitable sweetener substitutes for specific food products and support calorie reduction efforts.

This study looked at the differences in oxygen use when cells are nourished with glucose versus galactose. They saw a significant increase in oxygen utilisation with galactose, allowing them to characterise metabolic changes in diabetic patients, thereby creating a new model for the molecular mechanisms of mitochondrial dysfunction.

American Journal of Clinical Nutrition published this study demonstrating the fat burning benefits of galactose: “Galactose consumption is associated with higher endogenous fat mobilization and oxidation during meal absorption”

This study aimed to identify metabolic pathways associated with different metabolic characteristics in obesity. Subjects with metabolic healthy obesity (MHO) and metabolic abnormal obesity (MAO) were analyzed using metabolomic profiling. Significant differences in metabolites and pathways were found between the MHO and MAO groups, providing insights into the development of abnormal metabolic phenotypes in obesity.

Early human studies suggested tagatose as a potential antidiabetic drug through its beneficial effects on postprandial hyperglycaemia and hyperinsulinaemia. A subsequent 14-month trial confirmed its potential for treating type 2 diabetes, and tagatose showed promise for inducing weight loss and raising high-density lipoprotein cholesterol, both important to the control of diabetes and constituting benefits independent of the disease.

Obesity leads to enlarged adipose tissue, and contrary to previous understanding, mature human adipocytes can enter an active cell cycle. However, chronic hyperinsulinemia triggers premature cell cycle exit and senescence in adipocytes. Targeting the adipocyte cell cycle with metformin may help reduce obesity-related inflammation.

This study investigated how adding resistant starch (RS), a type of dietary fiber, to the diet might help people with overweight or obesity. They conducted a trial with 37 participants and found that taking RS supplements for 8 weeks led to weight loss (an average of 2.8 kilograms) and improved insulin resistance. These benefits were linked to changes in the composition of gut bacteria. Specifically, a type of bacteria called Bifidobacterium adolescentis seemed to play a key role. When this bacteria was supplemented in male mice, it protected them from becoming obese on a high-calorie diet. The study suggests that RS alters the gut bacteria, which in turn affects various processes in the body such as bile acid levels, inflammation, and fat absorption, ultimately aiding in weight loss. This highlights the importance of gut bacteria in the beneficial effects of RS on weight loss and metabolic health.