INTRODUCTION:

Probiotics are live organisms, particularly bacteria intended to have health advantages if consumed in an appropriate quantity¹. Probiotics use is not a novel entity. Millions of humans use probiotic dietary supplements to improve their digestive health. Probiotics, fermented foods are part of vitamins in South Indian food tradition.

The liver plays pivotal function in detoxing and in substrate metabolism. It is obvious that the composition of bacterial components in the intestine may want to affect the functioning of the liver².

Few studies showed probiotics are powerful, however at the same time, one study reported that many human being’s digestive tract prevent normal probiotics from efficaciously colonizing bacteria². The “gut – liver” axis has a huge function in the pathophysiology of numerous hepatic diseases³. Probiotics enables to modulate the immune system in the intestine via luminal conversion process⁴. Probiotics may additionally alter gut microbiota and may change pathogenic interactions in chronic liver disease^4,5. They might also repair the composition of the intestine microbiome and induces beneficial features to gut microbial communities resulting in enhancement or prevention of intestine inflammation and different intestinal or systemic diseases⁶.

Factors affecting the composition of gut microbiota:

The intestine microbiota function in human health have been pronounced in many animal⁷ and human studies⁸. Variety of factors (Figure 1) have an effect on the development and alteration of the intestine microbiome such as host immunity, genetic elements, age⁹, nutritional pattern, lifestyle, malnutrition, mode of birth¹⁰ and consumption of antibiotics¹¹and different medications.

Fig: 1 Factors affecting the composition of gut microbiota

Major function of human gut microbiota in health and illness:

The gut microbiome plays fundamental roles in both the protection of health and the pathogenesis of illnesses. Many researchers have given a perception about intestine microbiome and their metabolome. Functions of intestine microbiota are many which encompass metabolic, digestive and immunological functions⁵ (Figure 2). It provides host’s nutritional requirements through complex carbohydrate metabolism, and synthesis of vitamin K and complements the production of antimicrobial agents¹². Colonic microbes can make “short chain fatty acids (SCFAs) including butyrate, acetate and propionate” through polysaccharide metabolism and were reported to have a direct function in the augmentation of gut's epithelial cells barrier function and subsequent protection in opposition to pathogens by way of Peyer's patches formation, mucosal lymphoid follicles and plasma cells which secretes antibodies¹³. Butyrate is providing the predominant source of energy for colonocytes. The energy produced can be various with alterations in intestine microbiota and this extra energy accumulation has been implicated to cause weight problems in adults⁵. SCFAs are identified with a property to fight against inflammation in matured intestinal cells (enterocytes) and immunocytes. SCFAs generated by enteral commensal colonizing bacterial action with human milk also have ability to fight against inflammation in not fully matured human ‘enterocytes’¹⁴.

The intestine microbiota dwelling in gastrointestinal tract induces essential health protection with the aid of regulating both innate and adaptive immune homeostasis in the host. Any changes of those microbial flora can cause immune dysregulation and later on autoimmune disorders¹⁴. The interaction between gut microbiota and the “toll like receptors (TLRs)”, and “Nod like receptors (NLRs)” helps to hold intestinal immunity homeostasis¹⁵.

Fig-2 Functions of gut microbiota

Gut microbiota in liver disease:

Liver diseases are a major global health concern with high morbidity and mortality. Around 10 lakh patients of liver cirrhosis are newly recognized each annually in India. As in line with WHO, liver disorder is the 10th leading cause of death in India¹⁶. Cirrhosis of liver is the 14^th main cause of deaths within the world by 2020. Many researches recently showed that microbiota has been involved in the pathology of hepatic disease. The constituents of intestinal microbiome and its metabolites take part in a critical function in “gut-liver axis” like abolish oxidative reactive stress, reduces infection and preventing of liver fat deposition¹⁷. Hence, the intestinal microbiome might be a hopeful target to avoid and regulate the progression of hepatic sickness.

From the hepatic portal gadget, the liver gets a dual blood supply from the portal vein (75%) and hepatic arteries (25%). Oxygen is furnished from each sources in about half proportions. Immune cells present in hepatic sinusoids can clear out micro-organism and their by-products effectively from the portal blood circulation, thus protecting the person from endotoxemia. Endotoxemia results in liver damage with TLR interactions which in addition set off immune and inflammatory responses¹². Changes in microbiota were mentioned in “alcoholic liver disease (ALD)”, “non-alcoholic fatty liver disorder (NAFLD)”/“non- alcoholic steatohepatitis (NASH)”, “hepatic encephalopathy (HE)”, liver cirrhosis and “hepatocellular carcinoma (HCC)”. In addition, changes in microbiota may impact the starting of liver disease, but also its progression to severity and complications chances.^12,18

Probiotics and related natural products:

The Greek word probiotics which means “for existence”, became brought within the early 20th century. Clinicians can modulate the gut microbial milieu through the usage of selective gut decontamination with lactulose or through the use of Bifidobacterium, and lactobacillusor by way of the usage of prebiotics, probiotics and synbiotics¹⁹. Probiotics are live micro-organism and yeasts generally provided within the form of spores in sufficient amount to get useful effects. Prebiotics are non-digestible food components with beneficial effects on the host by means of selectively set off the activity of restrained wide variety of micro-organism in colon to enhance health²⁰. Prebiotics are substrates that are fermented by means of the microbiota¹⁸. Synbiotics are combinations of prebiotics and probiotics.

Many natural nutritional products have the capacity in refining intestine mucosal integrity, modulating microbiota composition and eliminating harmful products and translocated micro-organism in the liver^21-23. Some of the natural items used are flax seed oil²⁴, brown algae lessonianigrescens²⁵ and epigallocatechin gallate in green tea²⁶. Useful natural microbiota, Lactobacillus plantarum usually present in all food items which is fermented had reported to reduce hepatic disease progression as a probiotic²⁷.

Non -alcoholic fatty liver disease (NAFLD):

NAFLD is emerging as a main reason for hepatic ailments and is mentioned as fat accumulation in the liver. Epidemiological studies stated a 9-32% incidence in the Indian general population with accelerated prevalence in obese, diabetic, and pre-diabetic patients ²⁸. Patients suffering with NASH are at high risk of progression to liver cirrhosis and/or changing to HCC. A study confirmed that BS15-dealt with high-fat weight loss plan (HFD) mice had been guarded from liver cell fat accumulation and programmed liver cell death and improving the liver antioxidant defense system in NAFLD patients. BS15 decreased the serum lipopolysaccharide levels in mice with NAFLD by decreasing the permeability of gastrointestinal tract and modifying the intestine micobiota, accompanied by means of the decreasing the level of TNFα mRNA in the liver and serum C-reactive protein levels; suggesting that BS15 might be beneficial in averting NAFLD persuade by high fat diet²⁹. Some natural items have proven hopeful results on hepatic pathogenesis. Randomized clinical trials conducted recently proposed that probiotics could improve transaminases levels and hepatic steatosis and decrease liver inflammation³⁰. The most usually used probiotics in many recent scientific trials are Lactobacilli, streptococci, and bifidobacterial. Many trials have proven that probiotic use has therapeutic effects in fatty liver mice models³⁰. Many human trials carried out have been small-scale with mixed results. However, the common outcome with the use of probiotics/synbiosis might point to a promising therapeutic intervention for NAFLD patients by improving the clinical wellness, influencing insulin sensitivity, and decreasing TNF-α^31-46. A Xiao MW et al. meta-analysis showed probiotics' impact on liver characteristics in NAFLD patients. Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) levels were substantially reduced within the probiotics group but showed no correlation between TNF-α and probiotics⁴⁷. Insulin resistance (IR) and hyperinsulinemia are strongly related to NAFLD, and IR has negative results on hepatic metabolism⁴⁸. Further, it confirmed a promising beneficial impact of probiotics on insulin levels and IR, but a non-significant reduction in fasting blood sugar⁴⁷. Ongoing research may additionally supply greater insight into this element in near future.

Other liver diseases:

Cirrhosis:

Gut flora alterations had been mentioned in progressive hepatic ailments such as cirrhosis with or without complications⁴⁸. Probiotic use has been analysed in persons with compensated cirrhosis with complications. Recent trials revealed that probiotics can induce intestinal immunity, reduce bacterial translocation and systemic inflammatory status in patients with liver cirrhosis along with portal hypertension⁴⁹. Oral intake of Saccharomyces boulardii enhances carbon tetrachloride (CCl4) effected hepatic fibrotic changes in mice through decreasing the permeability of intestines, normalizes the cytokine levels (pro-inflammatory) and attenuating gut microbiota and treatment by this probiotic. Yeast may additionally slow down the progression of liver fibrosis ⁵⁰.

Hepatocellular carcinoma (HCC):

The HCC, is the extreme hepatic disease of chronic nature. Transformed gut microbiome and the presence of endotoxins in the blood (endotoxemia) are augmenting more and identified as crucial constituents in favouring the disease advancement to HCC. Probiotics are recommended as a new, safe and cost-effective approach to prevent or treat HCC. Probiotics exert their anti- cancer mechanism by their potential to bind carcinogens, attenuation of human intestinal microbiota, refinement of ‘intestinal barrier function, and immunomodulation’⁵¹. Recent research projected that particular intestine microbiota fingerprint may be correlated with early HCC presentation, and indicating that bacterial metabolites along with deoxycholic acid (DCA) can favour hepatic cell carcinogenesis through the damage of hepatocellular DNA and liver inflammation⁵². Natural prebiotic products like inulin-type fructans revealed antiproliferative impacts on HCC through gut microbiota modulation and gut-derived SCFA production¹⁷. Probiotics observe shielding effects at the intestinal mucosa and modulate immune responses.

In general, many research studies pointed out that probiotics might be beneficial in the stimulation of the immune system, avoidance of allergic diseases, control of GI tract inflammatory diseases and malignancy prevention⁵³. Lactobacilli as a probiotic have been used as an useful therapy for management of several pathological conditions displaying an overall positive safety profile^54,55. Generally claimed values of probiotics are decrease of potentially harmful gastro-intestinal microorganisms, modification of the bowel regularity, declining of flatulence and bloating, the safeguarding of lipids and proteins from oxidative damage, and maintenance of individual intestinal microbiota in those persons on antibiotics⁵⁶. The most-studied species include Lactobacillus, Bifidobacterium, and Saccharomyces which may re-establish normal microbiota and effect the functioning of the gastrointestinal tract by many mechanisms⁵⁷.

CONCLUSION:

Gut microbiota has a prominent role in liver ailment pathogenesis. Supplementation of probiotics can be a secure and cost effective approach in the liver disease management. Most of the facts about probiotics is derived from research on animals. More human studies with large populations are necessary for translating this evidence into clinical practice. Human studies are required to assess the right dose, duration, and any side effects probiotics might have. Clinical trials can be performed to evaluate the effectiveness of natural food items by means of modulating the gut microbiota in people with liver illnesses. More number of detailed human clinical trials are needed to understand better the impact of microbiota-host interactions, and its effect on health, and to rule out the feasible use of bacterial strains selectively as a therapeutic entity in the treatment of liver diseases.

AUTHOR CONTRIBUTIONS:

Conceptualisation and writing – Safeena Beevi. S. S, Biju Pottakkat. Review and editing- Biju Pottakkat, Sankar Narayanan

FUNDING:

The author(s) received no financial support for the research, authorship, and/or publication of this article.

CONFLICTS OF INTEREST:

The authors declare no conflict of interest

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Received on 19.12.2022 Modified on 26.02.2023

Asian J. Nursing Education and Research. 2023; 13(2):157-161.

DOI: 10.52711/2349-2996.2023.00034