Butyric acid has been shown to reduce high-fat diet-related metabolic disturbances and to improve intestinal barrier function due to its potent anti-inflammatory capacity. This study investigates whether a butyric acid ester, monobutyrin (MB) affects lipid profiles and gut barrier function in a dose-response manner in rats fed butter- or lard-based high-fat diets. Four-week-old male Wistar rats were fed butter-based diets containing 0, 0.25, 0.75 and 1.5 MB g/100 g (dry weight basis) or 0.5 glycerol g/100 g, and diets with lard (La) containing 0 and 0.5 MB g/100 g or a low-fat control diet for 3–4 weeks. Lipid profiles in blood and liver tissue, intestinal permeability and cecal short-chain fatty acids were examined. The results showed a dose-dependent decrease in liver total cholesterol for 1.5 MB (p < 0.05) and liver triglycerides for 0.75 MB (p < 0.05) and 1.5 MB (p = 0.08) groups compared to the high-fat control group. Furthermore, a lower excretion of mannitol in urine in the 1.5 MB group indicated improved intestinal barrier function. When MB was supplemented in the lard-based diet, serum total cholesterol levels decreased, and total amount of liver high-density lipoprotein-cholesterol increased. Thus, MB dietary supplementation can be effective in counteracting lipid metabolism disturbances and impaired gut barrier function induced by high-fat diets.

Lingonberries (LB) have been shown to have beneficial metabolic effects, which is associated with an altered gut microbiota. This study investigated whether the LB-induced improvements were associated with altered gut- and neuroinflammatory markers, as well as cognitive performance in ApoE−/− mice fed high-fat (HF) diets. Whole LB, as well as two separated fractions of LB were investigated. Eight-week-old male ApoE−/− mice were fed HF diets (38% kcal) containing whole LB (wLB), or the insoluble (insLB) and soluble fractions (solLB) of LB for 8 weeks. Inclusion of wLB and insLB fraction reduced weight gain, reduced fat deposition and improved glucose response. Both wLB and insLB fraction also changed the caecal microbiota composition and reduced intestinal S100B protein levels. The solLB fraction mainly induced weight loss in the mice. There were no significant changes in spatial memory, but significant increases in synaptic density in the hippocampus were observed in the brain of mice-fed wLB and insLB. Thus, this study shows that all lingonberry fractions counteracted negative effects of HF feedings on metabolic parameters. Also, wLB and insLB fraction showed to potentially improve brain function in the mice.

Monobutyrin (MB) and monovalerin (MV), esters of short-chain fatty acids (SCFAs), have previously been shown to reduce liver cholesterol and inflammation in conventional rats fed high-fat diets. This study explored the potential effects of MB and MV in hypercholesterolemic apolipoprotein E-knockout (ApoE-/-) rats. ApoE-/- rats were fed three high-fat (HF) diets, pure or supplemented with MB or MV (1%), for 5 weeks. One group of conventional rats (C) was also fed the pure high-fat diet and another group of ApoE-/- rats a low-fat (LF) diet. Blood and liver lipids, urinary lactulose/mannitol, SCFAs (blood and brain), tight junction proteins (small intestine and brain), and inflammation-related markers (blood, brain, and liver) were analyzed. MV supplementation elevated serum high-density lipoprotein (HDL) cholesterol and valeric acid concentration (p < 0.05), while the amounts of isovaleric acid in the brain were reduced (p < 0.05). MB increased butyric acid amounts in the brain, while the plasma concentration of interleukin 10 (IL-10) was lowered (p < 0.05). Both MV and MB upregulated the expression of occludin and zonula occludens-1 (ZO-1) in the brain (p < 0.05). Supplementation of MB or MV affected HDL cholesterol, the expression of tight junction proteins, and SCFA profiles. MB and MV may therefore be promising supplements to attenuate lipid metabolic disorders caused by high-fat intake and genetic deficiency.

Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose-manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were fed bromelain or papain in a dose of 1 mg per animal/day for three consecutive days, followed by the assessment of digestive protein capacity, intestinal morphology and gut microbiota composition. Furthermore, a human reconstructed 3D tissue model EpiIntestinal (SMI-100) was used to study the effects of 1, 0.1 and 10 mg/mL doses of each enzyme on tissue integrity and mucosal permeability using TEER measurements and passage of Lucifer Yellow marker from the apical to the basolateral side of the mucosa. The results indicated that fruit proteases have the potential to modulate gut microbiota with decreasing abundance of Proteobacteria and increasing beneficial Akkermansia muciniphila. The enhancement of pancreatic trypsin was observed in bromelain and papain supplementation, while bromelain also increased the thickness of the ileal mucosa. Furthermore, an in vitro study showed a dose-dependent interruption in epithelial integrity, which resulted in increased paracellular permeability by the highest doses of enzymes. These findings define bromelain and papain as promising enzymatic supplementation for controlled enhancement of paracellular uptake when needed, together with beneficial effects on the gut microbiota.

Background: Precocious maturation of the gastrointestinal barrier (GIB) in newborn mammals can be induced by dietary provocation, but how this affects the gut microbiota and the gut‐brain axis remains unknown. The objective of this study was to investigate effects of induced GIB maturation on gut microbiota composition and blood‐brain barrier (BBB) permeability.Methods: Suckling rats were studied at 72 h after gavage with phytohemagglutinin (PHA) or microbial protease (PT) to induce maturation of GIB. For comparison, untreated suckling and weaned rats were included (n = 10). Human serum albumin (HSA) was administered orally and analyzed in blood to assess permeability of the GIB, while intraperitoneally injected bovine serum albumin (BSA) was measured in the brain tissue for BBB permeability. The cecal microbial composition, plasma lipopolysaccharide‐binding protein (LBP) levels and short‐chain fatty acids in serum and brain were analyzed.Key Results: Cessation of HSA passage to blood after PHA or PT treatment was similar to that seen in weaned rats. Interestingly, concomitant increases in cecal Bacteroidetes and plasma LBP levels were observed after both PHA and PT treatments. The BBB passage of BSA was surprisingly elevated after weaning, coinciding with lower plasma LBP levels and specific microbial taxa and increased acetate uptake into the brain.Conclusions & Inferences: This study provides evidence that the gut microbiota alteration following induced precocious GIB maturation may induce low‐grade systemic inflammation and alter SCFAs utilization in the brain which may also play a potential role in GIB‐BBB dysfunction disorders in neonates.

The health benefits of bean consumption are widely recognized and are largely attributed to the dietary fiber content. This study investigated and compared the effects of whole brown beans and an isolated bean dietary fiber fraction on the plasma lipid profile, atherosclerotic plaque amount, gut microbiota, and microbiota-dependent metabolites (cecal short-chain fatty acids (SCFAs) and plasma methylamines) in Apoe^−/− mice fed high fat diets for 10.5 weeks. The results showed that both whole bean and the isolated fiber fraction had a tendency to lower atherosclerotic plaque amount, but not plasma lipid concentration. The whole bean diet led to a significantly higher diversity of gut microbiota compared with the high fat diet. Both bean diets resulted in a lower Firmicutes/Bacteroidetes ratio, higher relative abundance of unclassified S24-7, Prevotella, Bifidobacterium, and unclassified Clostridiales, and lower abundance of Lactobacillus. Both bean diets resulted in higher formation of all cecal SCFAs (higher proportion of propionic acid and lower proportion of acetic acid) and higher plasma trimethylamine N-oxide concentrations compared with the high fat diet. Whole beans and the isolated fiber fraction exerted similar positive effects on atherosclerotic plaque amount, gut microbiota, and cecal SCFAs in Apoe^−/− mice compared with the control diets.