Leaky Gut and Probiotics

Leaky Gut and Probiotics

Can Probiotics affect the intestinal barrier?

Probiotics are helpful in preserving the gut barrier function and alleviating the symptoms of the so called leaky gut syndrome in a variety of disorders including ulcerative colitis, liver injury, alcohol intoxication and stress.

The intestinal barrier and its association with certain diseases

The gastrointestinal tract constitutes the largest interface between a person and his or her environment. The existence of an intact intestinal barrier is thus essential in maintaining health. This barrier regulates the trafficking entry of food macromolecules and harmful content from the intestinal lumen into the circulation.

Leaky Gut and Probiotics

The basic gastrointestinal barrier is composed of the intestinal epithelium, a single layer of cells lining the digestive tube and tied to one another by tight junctions, which seal the spaces between the cells. The entire gastrointestinal epithelium is coated with mucus, which is synthesized by cells that form part of the epithelium. Mucus serves an important role in mitigating shear stresses on the epithelium and contributes to barrier function.

The so called “leaky gut” consists of increased intestinal barrier permeability and a deranged passage of substances and bacterial components into the bloodstream.

Local infections by bacteria and viruses, exposure to toxins, stress, antibiotics or physical insults, and a variety of systemic diseases lead to increased intestinal barrier permeability. Such problems can be mild and readily repaired, or massive and fatal.

The disruption of the intestinal barrier could result in local or systemic immune-mediated diseases, such as Celiac disease, Crohn’s disease, Ulcerative colitis, food allergies, type-1 diabetes mellitus, autoimmune diseases and even mood disturbances.

Thus, the intestinal barrier functions as an interface between health and disease.

Leaky Gut Treatment – The relation between gut bacteria and intestinal permeability

The human gut is comprised of a large, diverse, and dynamic microbiota. The term microbiota describes 200 to 500 different bacterial species that colonize the outer and inner surfaces of the human body. There is increasing evidence suggesting that gut microbiota tightly regulates intestinal barrier function.

Probiotics, which were first reported more than 100 years ago and they defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” have attracted interest given the possibility of positively altering the intestinal microbiota composition and its interactions with the immune system and gut epithelium.

Probiotic bacteria can enhance barrier integrity

Convincing body of evidence indicates that probiotics are helpful in preserving the gut barrier function and alleviating the symptoms in a variety of disorders including ulcerative colitis, liver injury, alcohol intoxication and stress.

Ulcerative colitis (UC)

Multiple studies have been done recently on the use of probiotics as an adjuvant therapy for induction and maintenance of remission in UC:

  • The administration of L. plantarum and Lactobacillus reuteri in a colitis animal model decreased intestinal permeability .
  • Bifidobacteriumspecies improve the intestinal integrity in a rat model of colitis.
  • The probiotic mixture VSL#3, a multibacterial probiotics composed byBifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. bulgaricus, and Streptococcus thermophilus protected the intestinal epithelial barrier against acute colitis in a murine model.
  • Patients with UC that received higher doses of the beneficial bacteria Escherichia coli Nissle were found to have significantly higher remission rates as compare to those treated with lower dose or placebo [1].
  • UC patients with mild to moderate disease activity that used oral administration of VSL#3, showed a better rate of clinical remission as compared to the placebo group [2-3].

Nonalcoholic fatty liver disease (NAFLD)

NAFLD is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. Given that the gut and liver are connected by the circulatory system, it makes the liver more vulnerable to translocation of bacteria, bacterial products or dotoxins. Altered intestinal microbiota may stimulate hepatic fat deposition by regulation of gut permeability. The probiotic mixture VSL#3 prevented the increased permeability as well as the elevated translocation and the liver injury in an acute liver injury mice model.

Human studies showed that VSL#3 was well tolerated, improved conventional liver function tests and reduced the levels of markers of lipid peroxidation and/or TNF-α. The treatment also induced a reduction in stress markers [4]. A recent meta-analysis concluded that probiotic therapies can reduce liver aminotransferases, total cholesterol, and TNF-α and improve insulin resistance in nonalcoholic fatty liver disease patients [5].

Alcoholic liver disease (ALD)

ALD is associated with an increased translocation of bacteria from the gut as well as endotoxemia, which could partly depend on gut leakiness mediated by increased oxidative stress. The therapeutic effects of probiotic treatment in ALD have been studied in both patients and experimental animal models. The administration of L. rhamnosus in a study of alcohol injury in the rat reduced the alcohol-induced intestinal leakage and decreased oxidative stress in both small intestine and colon.

An investigation performed in a randomized group of 66 alcoholic male patients and 24 healthy, adult male showed that alcoholic patients had reduced numbers of Lactobacilli and Enterococci, and increased number of E. coli. The alcoholic patients, who received probiotics, restore the levels of depressed numbers of Bifidobacteria, Lactobacilli, and Enterococci to that seen in healthy controls. Initial liver function tests, specifically AST, ALT, and GGT, were significantly elevated in the alcoholic group. After 5 days of probiotic therapy, patients treated with probiotics had significantly lower AST and ALT activity compared to the control group [6].

Stress

Stress is known to affect gastrointestinal functions, such as gut motility, and to impair the barrier function. Animal models of both acute and chronic stress have been developed with manifestations of enhanced bacterial adherence to and internalization of the gut wall, increased translocation and altered gut permeability. L. paracasei improved stress-induced visceral pain and restored normal gut permeability in the maternal stress model. In a human clinical study, L. helveticus and B. longum taken in combination display beneficial psychological distress in healthy human volunteers [7].

Conclusion: Leaky Gut and Probiotics

These results indicate that dietary addition of probiotic mixture is effective in restoring the integrity of intestinal barrier function in diverse gut barrier associated disorders such as ulcerative colitis, liver diseases and stress.

Research Resources: Leaky Gut and Probiotics

  1. Matthes H, Krummenerl T, Giensch M, Wolff C, Schulze J. Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN)BMC Complement. Altern Med. 2010;10:13.
  2. Sood A, Midha V, Makharia GK, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis.Clin Gastroenterol Hepatol.2009; 7(11):1202–1209.
  3. Tursi A, Brandimarte G, Papa A, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study.  Am J Gastroenterol.2010; 105(10):2218–2227.
  4. Loguercio C, Federico A, Tuccillo C, Terracciano F, D’Auria MV, De Simone C, Del Vecchio Blanco C. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005; 39(6):540-3.
  5. Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis.World J Gastroenterol. 2013; 19(40):6911-8.
  6. Kirpich I. A., Solovieva N. V., Leikhter S. N., Shidakova N. A., Lebedeva O. V., Sidorov P. I., et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 2008; 42, 675–682.
  7. Messaoudi M1, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011; 105(5):755-64.

Avi TrevesLeaky Gut and Probiotics