Probiotics

Probiotics was first conceptualized by the Russian Nobel Prize winner and father of modern immunology- Elie Metchnikoff at the beginning of the 20th century. He believed that the fermenting bacteria in milk products consumed by Bulgarian peasants were responsible for their longevity and good health. Recent research is now catching up with what he already knew. The actual word was first used by Lilly and Stillwell in 1965 as a contrast to the word “antibiotics”.

Probiotics were defined by a group of experts convened by the Food and Agriculture Organization of the United Nations (FAO) as “live microorganisms administered in adequate amounts which confer a beneficial health effect on the host”. Most probiotics are bacteria.

Human beings are associated with a large and diverse population of microorganisms that live on body surfaces and in cavities connected with the external environment. The skin, mouth, vagina, upper respiratory tract, and gastrointestinal tract of humans are inhabited by site-specific microbial communities with specialized structures and functions. ‘Microbiota’ is a collective term for the microbial communities in a particular ecological niche. Thus, the term ‘gut microbiota’ refers to the ecosystem of microorganisms that have adapted to live on the intestinal mucosal surface or within the gut lumen.

In humans, the gastrointestinal tract houses around two hundred trillions of microbial cells with over 1,000 diverse microbial species, most of them belonging to the domain Bacteria. Microbial communities in the gut include native species that colonize the intestine permanently, and a variable set of living microorganisms that transit temporarily through the gastrointestinal tract. On the other hand, the mucosa of the gastrointestinal tract constitutes a major interface with the external environment, and is the body’s principal site for interaction with the microbial world.

The normal interaction between gut microbes and their host is a symbiotic relationship, defined as mutually beneficial for both partners. The host provides a nutrient-rich habitat, and intestinal microbes confer benefits on the host’s health. The distal intestine represents an anaerobic bioreactor programmed with an enormous population of microbes. Due to the slow transit time of colonic contents, resident micro- organisms have ample opportunity to degrade available substrates, which consist of non-digestible dietary residue and endogenous secretions.

Lactic acid producing genera such as the bifidobacteria or lactobacilli have a long- standing association with health. These bacteria can be increased either by feeding appropriate strains as a probiotic or through the provision of prebiotic growth substrates.

To be effective, probiotics must be capable of being prepared in a viable manner and on large scale (e.g. for industrial purposes), whilst during use and under storage the probiotic should remain viable and stable. For most applications they should be able to survive in the intestinal ecosystem and the host animal should gain beneficially from harboring the probiotic. Clearly, the organisms used should be generally regarded as safe.

Protective Functions

An important function of the gut microbiota is the barrier effect that prevents invasion by pathogens. Resident bacteria represent a resistance factor to colonization by exogenous microbes or opportunistic bacteria that are present in the gut, but their growth is restricted. The equilibrium between species of resident bacteria provides stability in the microbial population, but antibiotics can disrupt the balance (for instance, overgrowth of toxigenic Clostridium difficile). Several mechanisms are implicated in the barrier effect.
Bacteria compete for attachment sites in the brush border of intestinal epithelial cells. Adherent non-pathogenic bacteria can prevent attachment and subsequent entry of pathogenic entero-invasive bacteria into the epithelium. Finally, bacteria can inhibit the growth of their competitors by producing antimicrobial substances called bacteriocins. The ability to synthesize bacteriocins is widely distributed among microbial collectivities of the gastrointestinal tract.

The Gut Microbiota in Functional Bowel Disorders

The functional bowel disorders (FBDs) are a group of highly prevalent digestive disorders in which symptoms are attributable to the mid and lower intestinal tract. The most common FBD are the irritable bowel syndrome (IBS), functional bloating, functional diarrhoea, and functional constipation.

FBDs are associated with reduced quality of life in affected patients and high social costs. The term functional was originally introduced to support the concept that these disorders are characterized by gut dysfunction in the absence of organic causes identifiable by common investigations. Psychological factors (e.g., anxiety, depression) abnormal gut motor patterns and increased visceral sensitivity are key elements in the pathophysiology of most FBD.

Recent growing evidence indicates that subtle, organic abnormalities can be detected along the brain-gut axis, including the intestinal tract, the central nervous and the neural-hormonal system connecting them. These abnormalities include altered composition of the luminal milieu, dysfunction of epithelial tight junctions leading to increased intestinal permeability, abnormal gut endocrine system signaling and low-grade mucosal inflammation.

Most data linking microbiota to FBD have been obtained in patients with IBS. A current working hypothesis suggests that changes in gut microbiota participate in abnormal fermentation of dietary substrates, predominantly carbohydrates. Microbiota would also elicit excessive stimulation of the mucosal immune system through a leaky gut. The consequent low-grade inflammation and release of inflammatory mediators would ultimately affect gut motor responses and elicit visceral hypersensitivity. This view and the participation of microbial factors in the pathogenesis of FBD are supported by the following evidence:

• First, about 10% of episodes of acute infectious gastroenteritis lead to the onset of IBS, (so called post-infectious IBS).
• Second, subsets of patients show both qualitative and quantitative changes and instability over time of the microbiota.

Third, patients with IBS have increased circulating antibodies against flagellin, a component of indigenous bacteria inhabiting the human gut. They also have increased fecal levels of human beta-defensin-2, an antimicrobial protein produced by the gut mucosa (i.e., by Paneth cells) and mucosal expression of specific microbial receptors (called Toll-like receptors, TLRs).

Fourth, the modulation of gut microbiota with probiotics and non-absorbable antibiotics has been shown to improve symptoms over placebo, at least in subgroups of patients with IBS. Conversely, systemic antibiotics may induce or worsen IBS symptoms. Taken together, these data provide a proof of concept implicating intestinal bacteria-host interactions in pathophysiology and symptom generation in patients with IBS.
The Gut Microbiota in Inflammatory Bowel Disease

Antibiotic-associated diarrhoea

Some of the best evidence in support of probiotic health benefits is in the treatment of antibiotic-associated diarrhoea(AAD). Antibiotics are a common treatment for children, and 20% of antibiotic-treated children develop diarrhoea. AAD results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhoea as a result. The preventive role of some probiotics has been correctly assessed in randomly clinical trials. A review, assessing the work of 16 different studies representing more than 3400 patients’ evaluation, concluded that the evidence gathered suggested a protective effect of some probiotics in this condition.

Benefits

Probiotic organisms have several decided health benefits, which include:

• Bolster the immune system.
• Decrease the incidence and duration of diarrhoea, whether it is caused by antibiotics, Clostridium difficile, rotaviral, or other pathogens.
• Have anti-carcinogenic, anti-mutagenic, and anti-allergic activities.
• Help alleviate such inflammatory conditions as Crohn’s disease and ulcerative colitis.
• Help prevent colon cancer by preventing the breakdown of enzymes that contribute to the growth of cancer-causing agents.
• Help alleviate food, chemical, and/or environmental sensitivities.
• Improve digestion and balance cholesterol metabolism.
• Increase nutritional value of foods through better digestibility and an increased absorption of nutrients.
• Influence better intestinal and urogenital flora, especially after antibiotic and radiation therapies, which are known to induce colitis, yeast infections, and vaginitis.
• Maintain mucosal integrity.
• Manufacture lactase, which promotes intestinal lactose digestion.
• Prevent and reduce intestinal tract infections, including those caused by bacteria or viruses, Candida, and Helicobacter pylori.
• Provide an antagonistic environment for pathogens by normalizing beneficial organisms. This encourages friendly ones to crowd out of harmful ones, thereby blocking their adhesion sites in addition to inactivating enterotoxins.
• Reduce catabolic products (bile pigments) eliminated by kidney and liver.
• Reduce and eliminate overgrowth of small bowel bacteria.
• Regulate gut motility, thereby reducing such conditions as constipation.

Specific Probiotic Bacteria and Conditions

The following clinical probiotic studies have been reported as having beneficial effects:

• Normalize intestinal flora:Lactobacillus (acidophilus, casei, plantarum) and Bifidobacterium bifidum
• Stimulate the immune system:Lactobacillus (acidophilus, casei, rhamnosus, plantarum, delbrueckii, johnsonii) and Bifidobacterium bifidum
• Diarrhoea associated with antibiotics:Lactobacillus (rhamnosus, acidophilus, bulgaricus), Saccharomyces boulardii, Bifidobacterium longum, and Enterococcus faecium.
• Diarrhoea associated with traveling:Lactobacillus (rhamnosus, acidophilus, bulgaricus, johnsonii), Bifidobacterium bifidum, and Streptococcus (thermophilus, boulardii)
• Diarrhoea associated with the Rotavirus:Lactobacillus rhamnosus, Bifidobacterium bifidum, and Streptococcus thermophilus
• Acute diarrhoea:Bifidobacterium bifidum, Lactobacillus (bulgaricus, acidophilus, rhamnosus, reuteri) and Streptococcus thermophilus
• Recurring Clostridium difficile colitis:Lactobacillus (rhamnosus, boulardii)
• Anti-tumor properties:Lactobacillus (acidophilus, casei, plantarum, delbrueckii, gasseri) and Bifidobacterium (longum, bifidum, adolescentis, infantis)
• Reducing lactose intolerance:Lactobacillus (bulgaricus, rhamnosus, johnsonii) and Streptococcus thermophilus
• Lowering fecal enzyme activity:Lactobacillus (rhamnosus, casei, gasseri, delbrueckii, acidophilus)

References

Claudia Herrera andFrancisco Guarner, World Gastroenterology Organisation, Handbook On Gut Microbes 2014 p. 5-7

Giovanni Barbara, Cesare Cremon and Vincenzo Stanghellini, World Gastroenterology Organisation, Handbook On Gut Microbes 2014 p. 30-31