Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients, including glucose, amino acids, lipids, water, vitamins, and minerals within the small intestine. Recent advances in research, along with new cutting-edge technologies, have advanced our understanding of the mechanism of ethanol’s effect on intestinal nutrient absorption at the brush border membrane (BBM) of the small intestine. However, further studies are needed to delineate how ethanol consumption could have an impact on altered nutrient absorption under various disease conditions. Current research has elucidated the relationship of alcohol consumption on glucose, glutamine, vitamins B1 (thiamine), B2 (riboflavin), B9 (folate), C (ascorbic acid), selenium, iron, and zinc absorption within the small intestine. We conducted systematic computerized searches in PubMed using the following keywords: (1) “Alcohol effects on nutrient transport”; (2) “Alcohol mediated malabsorption of nutrients”; (3) “Alcohol effects on small intestinal nutrient transport”; and (4) “Alcohol mediated malabsorption of nutrients in small intestine”. We included the relevant studies in this review. The main objective of this review is to marshal and analyze previously published research articles and discuss, in-depth, the understanding of ethanol’s effect in modulating absorption of vital macro and micronutrients in health and disease conditions. This could ultimately provide great insights in the development of new therapeutic strategies to combat malnutrition associated with alcohol consumption.

Gastrointestinal health is influenced by the functional genes and metabolites generated by the human microbiome. As the volume of current biomedical and translational research indicates, the importance and impact of this ecosystem of microorganisms, especially those comprising the gut microbiome on human health, has become increasingly apparent. Changes to the gut microbiome are associated with inflammatory bowel disease (IBD), which is characterized by persistent intestinal inflammation. Furthermore, the lifetime dietary choices of their host may positively or negatively affect both the gut microbiome and its impact on IBD. As such, “anti-inflammatory” dietary supplements, their impact, and mechanisms in restoring gut microbiota homeostasis during IBD is an area of intensive research. Dietary supplementation may represent an important adjuvant treatment avenue for limiting intestinal inflammation in IBD. Overall, this review addresses the development of the gut microbiome, the significance of the gut microbiome in IBD, and the use of dietary supplements such as vitamin D, fish oil, and resveratrol in the mitigation of IBD-associated gut dysbiosis and intestinal inflammation.

In the chronically inflamed rabbit small intestine, brush border membrane (BBM) Na-glutamine co-transport is inhibited in villus cells (mediated by B0AT1), while it is stimulated in crypt cells (mediated by SN2/SNAT5). How mast cells, known to be enhanced in the chronically inflamed intestine, may regulate B0AT1 in villus and SN2/SNAT5 in crypt cell is unknown. Thus, the aim of the present study is to determine the regulation of B0AT1 and SN2/SNAT5 by mast cells during chronic enteritis. Chronic intestinal inflammation was induced in male rabbits with intra-gastric inoculation of Eimeria magna oocytes. Rabbits with chronic inflammation were treated with ketotifen (10 mg/day) or saline (Placebo) for 2 days. Villus and crypts cells were isolated from the rabbit intestine using the Ca++ chelation technique. Na/K-ATPase activity was measured as Pi from cellular homogenate. BBM vesicles (BBMV) were prepared from villus and crypt cells and uptake studies were performed using rapid filtration technique with 3H-Glutamine. Western blot analyses were done using B0AT1 and SN2 specific antibodies. In villus cells, Na-glutamine co-transport inhibition observed during inflammation was completely reversed by ketotifen, a mast cell stabilizer. In contrast, in crypt cells, Na-glutamine co-transport stimulation was reversed to normal levels by ketotifen. Kinetic studies demonstrated that ketotifen reversed the inhibition of B0AT1 in villus cells by restoring co-transporter numbers in the BBM, whereas the stimulation of SN2/SNAT5 in crypts cells was reversed secondary to restoration of affinity of the co-transporter. Western blot analysis showed that ketotifen restored immune-reactive levels of B0AT1 in villus cells, while SN2/SNAT5 levels from crypts cell remained unchanged. In the present study we demonstrate that mast cells likely function as a common upstream immune pathway regulator of the Na-dependent glutamine co-transporters, B0AT1 in villus cells and SN2 in crypts cells that are uniquely altered in the chronically inflamed small intestine.

The only Na‐nutrient cotransporter described in mammalian small intestinal crypt cells is SN2/SNAT5, which facilitates glutamine uptake. In a rabbit model of chronic intestinal inflammation, SN2 stimulation is secondary to an increase in affinity of the cotransporter for glutamine. However, the immune regulation of SN2 in the crypt cells during chronic intestinal inflammation is unknown. We sought to determine the mechanism of regulation of Na‐nutrient cotransporter SN2 by arachidonic acid metabolites in crypt cells. The small intestines of New Zealand white male rabbits were inflamed via inoculation with Eimeria magna oocytes. After 2‐week incubation, control and inflamed rabbits were subjected to intramuscular injections of arachidonyl trifluoromethyl ketone (ATK), piroxicam and MK886 for 48 hrs. After injections, the rabbits were euthanized and crypt cells from small intestines were harvested and used. Results: Treatment of rabbits with ATK prevented the release of AA and reversed stimulation of SN2. Inhibition of cyclooxygenase (COX) with piroxicam did not affect stimulation of SN2. However, inhibition of lipoxygenase (LOX) with MK886, thus reducing leukotriene formation during chronic enteritis, reversed the stimulation of SN2. Kinetic studies showed that the mechanism of restoration of SN2 by ATK or MK886 was secondary to the restoration of the affinity of the cotransporter for glutamine. For all treatment conditions, Western blot analysis revealed no change in SN2 protein levels. COX inhibition proved ineffective at reversing the stimulation of SN2. Thus, this study provides evidence that SN2 stimulation in crypt cells is mediated by the leukotriene pathway during chronic intestinal inflammation.

During chronic intestinal inflammation in rabbit intestinal villus cells brush border membrane (BBM) Na-glucose co-transport (SGLT1), but not Na/H exchange (NHE3) is inhibited. The mechanism of inhibition is secondary to a decrease in the number of BBM co-transporters. In the chronic enteritis mucosa, inducible nitric oxide (iNO) and superoxide production are known to be increased and together they produce abundant peroxynitrite (OONO), a potent oxidant. However, whether OONO mediates the SGLT1 and NHE3 changes in intestinal epithelial cells during chronic intestinal inflammation is unknown. Thus, we determined the effect of OONO on SGLT1 and NHE3 in small intestinal epithelial cell (IEC-18) monolayers grown on trans well plates. In cells treated with 100 μM SIN-1 (OONO donor) for 24 h, SGLT1 was inhibited while NHE3 activity was unaltered. SIN-1 treated cells produced 40 times more OONO fluorescence compared to control cells. Uric acid (1mM) a natural scavenger of OONO prevented the OONO mediated SGLT1 inhibition. Na⁺/K⁺-ATPase which maintains the favorable trans-cellular Na gradient for Na-dependent absorptive processes was decreased by OONO. Kinetics studies demonstrated that the mechanism of inhibition of SGLT1 by OONO was secondary to reduction in the number of co-transporters (V_max) without an alteration in the affinity. Western blot analysis showed a significant decrease in SGLT1 protein expression. Further, p38 mitogen-activated protein (MAP) kinase pathway appeared to mediate the OONO inhibition of SGLT1. Finally, at the level of the co-transporter, 3-Nitrotyrosine formation appears to be the mechanism of inhibition of SGLT1. In conclusion, peroxynitrite inhibited BBM SGLT1, but not NHE3 in intestinal epithelial cells. These changes and the mechanism of SGLT1 inhibition by OONO in IEC-18 cells is identical to that seen in villus cells during chronic enteritis. Thus, these data indicate that peroxynitrite, known to be elevated in the mucosa, may mediate the inhibition of villus cell BBM SGLT1 in vivo in the chronically inflamed intestine.