Thus, oats supplementation has to interfere with the physical, chemical, or metabolic effects, or a combination, of chronic alcohol. These effects include alcohol-induced changes in metabolic and signaling pathways responsible for gut leakiness and endotoxemia. We hypothesized that oats supplementation protects through its effects on oxidative pathways. We had two primary rationales for our hypothesis. First, it has been generally accepted that oats are of benefit to human health and normal gut growth and function not only because of their nutrient and fiber values but also because of their antioxidant and anti-inflammatory activities (Nie et al., 2006; Chen et al., 2007). Second, several studies have demonstrated the importance of oxidative stress and up-regulated iNOS in alcohol-induced tissue injury and organ dysfunction (Nanji et al., 1995; Sisson, 1995; Chow et al., 1998).
More specifically, several reports demonstrated the pivotal role of the up-regulation of iNOS and oxidative stress in alcohol-induced gut leakiness. For example,
our in vitro studies showed that preventing the up-regulation of iNOS that is induced by alcohol, using both iNOS inhibitors and dominant-negative mutant for iNOS, prevented alcohol-induced disruption of the barrier integrity of intestinal cell monolayers (Banan et al., 2000, 2001, 2007). Furthermore, we recently showed that inhibition of iNOS by l-N6-1-iminoethyl-lysine reduces EtOH-induced NO overproduction, oxidative tissue injury, and gut leakiness in alcohol-treated rats (Tang et al., 2009). Our current study, which uses immunohistochemical staining, provides direct evidence that EtOH induces iNOS activation in colonic epithelium and that oats prevent this effect and prevent alcohol-induced intestinal mucosal oxidative stress.
More specifically, several reports demonstrated the pivotal role of the up-regulation of iNOS and oxidative stress in alcohol-induced gut leakiness. For example,
our in vitro studies showed that preventing the up-regulation of iNOS that is induced by alcohol, using both iNOS inhibitors and dominant-negative mutant for iNOS, prevented alcohol-induced disruption of the barrier integrity of intestinal cell monolayers (Banan et al., 2000, 2001, 2007). Furthermore, we recently showed that inhibition of iNOS by l-N6-1-iminoethyl-lysine reduces EtOH-induced NO overproduction, oxidative tissue injury, and gut leakiness in alcohol-treated rats (Tang et al., 2009). Our current study, which uses immunohistochemical staining, provides direct evidence that EtOH induces iNOS activation in colonic epithelium and that oats prevent this effect and prevent alcohol-induced intestinal mucosal oxidative stress.
We also determined whether oats supplementation protects the cytoskeletal network in epithelial cells because our in vitro study, our in vitro study, using monolayers of intestinal epithelial cells, demonstrated that alcohol-induced leakiness is associated with disruption of both actin and microtubule cytoskeletons (Banan et al., 1999, 2000, 2001). We now show that oats prevents disorganization of actin and disruption of tight junctions. Moreover, our previous studies demonstrated that chronic, daily alcohol administration causes mild but detectable histological changes in intestinal mucosa of rat (Keshavarzian et al., 2001, 2009). In the present study, we show that alcohol-fed rats exhibit evidence of mild colonic inflammation with elevated mucosal MPO levels and that oats prevent alcohol-induced colonic inflammation. Thus, oats supplementation substantially attenuates these deleterious effects of EtOH on the colonic mucosa, preserves the architecture of the intestinal epithelium, protects the integrity of the intestinal barrier, and prevents gut leakiness.
Oats, like many other plant materials, contain numerous constituents—vitamins, minerals, essential fatty acids, β-glucan (fermentable fibers), and phytochemicals, including several phenolic compounds (Chen et al., 2007). These constituents have been found to possess many types of bioactivity, including antioxidant, antiproliferative, anti-inflammatory, and detoxification effects, which may contribute to the promotion of good health (Anderson and Hanna, 1999; Chen et al., 2007). Thus, the antioxidant effects of oats may not be limited to its ability to prevent up-regulation of iNOS. Therefore, in addition to the inhibition of EtOH-induced iNOS activation and NO overproduction in colonic mucosa, oats may also directly scavenge NO from other sources in the gut. EtOH can increase other oxidants such as OH- and CO-3, which may play an important role in the mechanism of gut leakiness (Nagata et al., 2007). The effect of oats on other oxidants needs to be further studied.
In addition, the beneficial effects of oats may not be limited to their antioxidant properties; their other bioactivities can contribute to their ability to prevent gut leakiness and endotoxemia. For example, the fermentable fiber component of oats, like any other fiber compounds, can affect intestinal microbiota composition and/or function (prebiotic effect). This effect can not only decrease the production of endotoxin by the gut lumen but also can affect alcohol metabolism by bacteria and thus affect the production of acetaldehyde. Because acetaldehyde is even more injurious to the intestinal barrier than alcohol (Rao et al., 2004), oats can prevent alcohol-induced disruption of the barrier, at least in part, by lowering the level of acetaldehyde in the colonic lumen of alcohol-fed rats. However, before we can consider the prebiotic effects of oats as a mechanism of its protection against alcohol injury to the intestinal barrier, we first need to demonstrate that alcohol causes abnormalities in gut microbiome composition and function (dysbiosis). Further studies are needed to assess gut microbiome in alcohol-fed rats and alcoholics.
Finally, studies are needed to identify the specific components of oats that are responsible for the protective effects of oats against alcohol-induced gut leakiness and endotoxemia.
Finally, studies are needed to identify the specific components of oats that are responsible for the protective effects of oats against alcohol-induced gut leakiness and endotoxemia.
In summary, we found that oats supplementation prevents EtOH-induced oxidative tissue damage and loss of intestinal barrier integrity. Our findings now provide a strong scientific rationale to test oats supplementation as a therapeutic strategy to prevent and/or treat gut leakiness in disorders such as ALD and inflammatory bowel disease in which oxidative stress is the key pathogenic factor. Clinical trials are needed to determine whether oats supplementation is useful for preventing and treating gut leakiness, endotoxemia, and liver injury in alcoholics.
