Lactobacillus Feeding Reduces Endotoxemia and Severity of Experimental Alcoholic Liver (Disease)

Abstract

We have previously shown a relationship between plasma endotoxin levels and severity of alcoholic liver injury in the intragastric feeding rat model. We attempted to reduce both circulating endotoxin and liver injury in this model by administering a lactobacillus strain (species GG) which survives for prolonged periods in the gastrointestinal tract. Male Wistar rats were fed ethanol and liquid diet containing corn oil (CO+E). Another group of animals (CO+E+L) received the diet containing ethanol plus a daily bolus of lactobacilli GG concentrate (10(10) CFU). All animals were sacrificed after one month. All animals had plasma endotoxin measurements and evaluation of severity of pathologic changes in the liver. The weight gain and blood alcohol levels were similar in both groups. The mean +/- SE of the pathology score was significantly higher (3.4 +/- 0.85) in the CO+E group compared to the CO+E+L group (0.5 +/- 0.3, P < 0.01). The virtual absence of pathologic changes in the latter group was accompanied by significantly lower endotoxin levels (8.4 +/- 2.9 pg/ml in CO+E+L group vs 48.3 +/- 7.8 pg/ml in CO+E group, P < 0.01). Feeding of strains of lactobacilli that survive in the gastrointestinal tract reduces endotoxemia and alcohol-induced liver injury in the rat. Lactobacillus species GG provides a potential nontoxic form of therapy for both endotoxemia and alcoholic liver disease.

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…In rats exposed to chronic ethanol in a liquid diet, administration of endotoxin led to the progression of liver injury from fatty liver to necro-inflammatory changes (Bhagwandeen et al, 1987;Pennington et al, 1997;Apte et al, 2005). In an intragstric infusion rat model of alcoholic liver injury, sterilization of intestine by antibiotics significantly attenuated liver injury by reducing plasma levels of endotoxin (Adachi et al, 1995), and in the same model, similar results were obtained by simultaneous feeding of probiotic lactobacillus GG bacteria (competitive inhibitor of Gram negative bacteria) to the rats (Nanji et al, 1994).…”

“…This connection was further confirmed when administration of LPS caused the progression of fatty liver into necroinflammatory changes in a rat model of alcoholic liver injury (Bhagwandeen et al, 1987;Pennington et al, 1997). In addition, elimination of intestinal bacteria or suppression of intestinal Gram negative bacteria attenuated alcoholic liver injury in rats by reducing plasma endotoxin levels (Adachi et al, 1995;Nanji et al, 1994). Normally, only a trace amount of endotoxin is absorbed from the intestine through the intestinal epithelial lining to the portal vein that carries it to the liver where it is cleared by Kupffer cells.…”

“…Serum endotoxin levels were elevated in rats with alcoholic liver injury developed after ethanol administration for 10 weeks by gavage (Keshavarzian et al, 2001). Similarly, plasma endotoxin levels were significantly elevated in rats with alcoholic liver injury developed in response to intragastric infusion of ethanol for 3-4 weeks (Nanji et al, 1994;Adachi et al, 1995). In mice, plasma endotoxin levels were significantly elevated 1.5 hour after intragastric administration of 6g/kg ethanol by gavage, and this was associated with significant small intestinal injury (Lambert et al, 2003).…”

“…Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG were shown to protect intestinal Caco-2 cells from the inflammation-associated response induced by Escherichia coli K88 (Roselli et al, 2006). Finally, in an intragastric infusion model of alcoholic liver injury, feeding of rats with Lactobacillus GG reduced plasma levels of endotoxin and severity of liver injury (Nanji et al, 1994). Whether probiotic treatment can attenuate ALD in humans needs further investigation.…”

Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4

“…1,2 In the Tsukomoto and French model of rat alcoholic hepatitis, 3 the degree of liver injury is diminished by treatment with either antibiotics, lactobacillus, or polymixin, all of which decrease endogenous LPS. 4,5 In this model, Kupffer cells, when activated by LPS, play a prominent role in promoting liver injury. 6 Despite its potentially critical importance, the molecular mechanism by which Kupffer cells are activated by LPS remains largely unknown.…”