Beneficial effect of prebiotics on gut microbiome and wellness

In recent years, the gut health has become a topic of concern for many. Compared to other parts of the body, the intestine harbours a large and complex flora comprising bacteria, viruses and fungi. The average flora in the intestine is 3.9×1013 that is more than the number of human cells in an adult. A healthy and balanced intestinal flora is crucial for the maintenance of health and well-being. This helps in better nutrient adsorption from food, regulates metabolism and the immune response by producing beneficial metabolites such as the amino acids, vitamins, short-chain fatty acids (SCFAs) and other substances. The intestinal flora can be divided into three categories based on their effect, probiotics – beneficial effect, neutral bacteria- no effect; pathogens- detrimental effect. Dysbiosys, an “imbalance” in the gut microbial community, may lead to lifestyle disease such as obesity, diabetes, IBS and even colon cancer. Therefore, it becomes necessary to maintain the balance through external supplementation of probiotic bacteria and prebiotics.

Probiotics 

Probiotics are defined as live microorganisms that, when administered in adequate quantities promote health and wellness. They exert beneficial effect on the intestinal health by maintenance of a healthy and balanced microflora, regulating the immune response, better digestion and adsorption of food, prevention of lactose intolerance and improvement of glucose metabolism. Not only the gut, the probiotics can positively impact the brain, skin, eyes and other organs and helps in overall well-being. There are certain important criteria for an efficient probiotic- survival at low gut pH, adhesion to the intestinal mucosa and the epithelial cells, utilize the prebiotic fibres and produce health benefitting metabolites. The probiotic mechanism of action involves prevention of pathogen growth, improvement in the gut barrier effect, production of metabolites that act as nerotransmitters and act on distal organs. The lactobacillus and the bifidobacteria are the most widely studied and most widely used probiotic bacteria.  

Lactobacill  are mostly present in fermented food and they have been studied through in vitro, in vivo and human clinical trials. Lactobacillus species such as L. plantarum, L. fermentum, L. gasseri, L. acidophilus etc. are used as commercial probiotics. Studies have documented the anti-inflammatory, anti-obesity, anti-diabetic effects of these probiotics.  Bifidobacterium is a specialized anaerobic bacteria that are ubiquitous inhabitant of the gastrointestinal tract. It has been named bifido as it exhibits  a “Y” shaped (bifid) morphology. It grows in the middle and end of the small and large intestine. It produces specific metabolites that maintains the intestinal health. 

Both Lactobacillus and Bifidobacteria are an important class of probiotics that find application in pharmaceutics, cosmetics. Other class of probiotics include the enterococcus, bacillus and saccharomyces species. 

How prebiotics help to improve the microbiota and maintenance of health? 

It is well known that the way to good health is through our GUT. Human intestine encompasses a wide variety of microorganisms called the intestinal microbiota. This intestinal microbiota plays a significant role in the maintenance of health and immunity.  The prebiotics can either directly affect the number and composition of the microbiota, or their metabolites, generated post fermentation, may induce additional benefits in the gut.  

There are multiple ways that prebiotics affect gut immunity, the first step being pathogen elimination. During intestinal-invasion, the pathogens bind to the epithelial cells followed by colonization. Prebiotics such as Fructo-oligosaccharide, Galactooligosaccharide,  Inulin  can act as decoy receptors that misleads the pathogen by mimicking  the pathogen –binding sites. The pathogens binds to these decoy or pseudo receptors and are eliminated from the gut.  

The prebiotic fibres serve as food for the probiotics, the fermentation by-products such as 

the short chain fatty acids (SCFA)  play a role in the maintenance of epithelial barrier integrity.  It has also been implicated in the maintenance of gut immune response

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Beneficial effect of Fructooligosaccharide  

Short-chain fructo-oligosaccharides (sc-FOS) are one of the most widely studied prebiotic fibres consumed by humans. Studies performed at preclinical and clinical level has clearly demonstrated the beneficial effect of the dietary fibre. Human trials have demonstrated that consumption of scFOS leads to an enrichment of the intestinal microflora. The Bifidobacteria and certain Lactobacillus possess certain innate enzymatic abilities that enable them to utilize scFOS for their growth. The stimulatory action of prebiotics (such as sc-FOS) on the immune system may occur via different mechanisms. 

Growth enhancement of Probiotics 

 It has been shown that a very low dose of scFOS is bifidogenic i.e it facilitates the growth of bifidogenic bacteria and lactobacilli. This helps in gaining a competitive advantage over pathogen colonization, acidification of colon through production of SCFA in the lumen. The SCFA positively impacts the components of the colonic immune system by activation of different pathways that includes- 

  • Activating the immune cells residing in the gut such as the immunity boosting T cells; dendritic cells, macrophages specializing in scavenging of potentially harmful microbes, apoptotic cells and cellular debris;  the natural killer (NK) cells having antiviral  and tumour immuno-surveillance property; and the neutrophils  that protect the host by targeting foreign particles that cross the epithelial barrier and enters the gut. 
  • Improvement in integrity of tight junction proteins that line the paracellular space between the intestinal epithelial cells and prevent the “leaky gut” syndrome, a condition that arise due to weakening of the intestinal walls resulting in leaching of bacteria and toxins into the bloodstream.  
  • SCFA such as butyrate are anti-inflammatory and helps in reducing inflammation and associated conditions such as inflammatory bowel disease (IBD) and colorectal cancer. Butyrate has also been reported to-induce mucin secretion that protects the intestinal lining from damage. 

Increased consumption of fat and low intake of fibres has resulted in increased susceptibility to gut associated inflammatory disorders.  Prebiotics positively impact the growth of probiotic bacteria and helps in rebiosis; in addition, the ability to balance the pro and anti-inflammatory response.  

Protection against diarrhoea 

 Prebiotics, such as scFOS, exhibit efficacy in preventing enteric diseases by selectively stimulating the growth of bifidobacteria and lactobacilli in the gut. In a trial involving children (1–14 years of age) suffering from acute diarrhoea, consumption of  sc-FOS (2.5–5 g/day) reduced the duration of diarrhoea events as compared to control group. In another trial comprising children (25 to 59 months) consumption of a solution of 2g scFOS daily for 6 months reduced the number of diarrhea episodes as compared to the placebo group. 

Protection against inflammation 

Inflammatory bowel disease occurs due to imbalance in the gut miroflora. Prebiotic fibres are attributed with the property of increasing the abundance of the beneficial bifido and lacto bacillus species in the intestine. This has been supported by in vivo and clinical studies. The lactobacilli helps in increasing lactate and butyrate which contributes to the beneficial effect of FOS in reducing of gut inflammatory conditions such as colitis. sc-FOS also helps to reduce the damage caused from oxidative stress and inflammation caused by improper or imbalanced diet. 

How interactions between prebiotics and probiotics act on different organ systems? 

The potential of the gut microbiome to impact distant organ sites is currently been investigated. The impacts on distant organs, such as the immune system, brain, and skin, have created the following research fields: gut-imune axis, gut–brain axis and gut–skin axis. 

The Gut-Immune axis: Effect on immune system 

 The human gut, comprising the GALT system (gut-associated lymphoid tissue),is the largest human immune tissue. It serves as the first line of defence against any pathogenic invasion. The intestinal immunity is influenced by the interactions between the microbiota and the GALT. The probiotic commensal bacteria release short chain fatty acids (SCFA) in the intestinal tract along with several other metabolites. Subsequently, they then act on the local as well as the systemic immune cells and the gut-associated epithelial cells. The cumulative effect results in the maintenance of the epithelial barrier integrity and modulation of innate immunity through secretion of cytokines, effect on immune cells such as the macrophage, neutrophils recruitment, dendritic cells and T cells. 

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The Gut-brain axis: Effect on the nervous system 

The gut-brain axis is a bidirectional communication network between the enteric and central nervous systems. It links the emotional and cognitive centres of the brain with peripheral intestinal functions.   Recent advances in research have described the significance of the gut microbiota in influencing these interactions. The signalling is bidirectional, initiates from gut-microbiota to brain and from brain to gut-microbiota and involves the neural, endocrine, immune, and humoral networks. Several mood disorders, such as anxiety, depression, and autism now have well-established links to the gastrointestinal functions and are associated with alteration of the gut microbiome. Studies have demonstrated that the composition of gut bacteria influences fetal and neonatal neurologic development. Diet has also been shown to a major role in the gut microbiome’s impact on cognitive function.  A new class of probiotics, known as psychobiotics or psychomicrobiotics, has emerged in the last decade and is being fervently embraced by many health care practitioners as a nontoxic intervention for various psychiatric conditions. Several clinical trials have evidenced the effect of probiotics  such as L acidophilus, B bifidum and B longum L casei for depression and anxiety.  

Gut-skin axis: Effect on skin functions 

The gut microbiome also impacts distal organs like the skin.  Pre- and probiotics aimed at the intestinal microbiome may be used for targeting skin health.  Consumption of   probiotic Lactobacillus reuteri , demonstrated shiny, thick and healthier looking fur in mice. Human trials have also validated reduced transepidermal water loss and skin sensitivity on probiotic consumption.  Studies have demonstrated the beneficial effect of probiotics  in the management of skin ailments such as,  acne vulgaris, atopic dermatitis, and psoriasis. Similar beneficial health effects have been determined by consuming prebiotics and synbiotics.

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Conclusion 

The human gut microbiome is largely unexplored and initiatives such as human gut microbiome initiative (HGMI) are undertaken by the scientific community to decipher the the microbial communities and predict redisposition towards various ailments such as diabetes, GI disorders, atopic disorders and other immunopathological conditions. The prebiotics and probiotics are been extensively explored for regulating the gut microbiome and influence the health and wellness. Studies have demonstrated that the consumption of prebiotic fibres change the intestinal microbiota. This establishes the importance of prebiotic fibres directed at influencing the gut microbiota for a beneficial effect on human health. Additionally, the prebiotics harbours the potential to either directly or indirectly modulate the host immune system. This immunomodulatory property of the prebiotics and probiotics has been exploited to develop potential applications in health and wellness products as well as adjunct immunomodulatory therapy for a wide variety of chronic disease conditions.

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