Abstract
Probiotics, originating at birth, play a crucial role in the development and maintenance of a healthy and disease-free environment within the gut of both humans and animals. These beneficial microorganisms from fermented, processed, and non-dairy foods provide numerous health benefits, such as stress reduction, disease prevention, immune stimulation, gut microbiota control, nutritional supplementation, diarrheal disease relief, vitamin production, weight management, and anticancer activities. With more health problems on the rise and the negative side effects of conventional medication and antibiotics prevailing, natural supplements such as probiotics are a relief. Probiotics, such as Lactobacillus, Bifidobacterium, and Saccharomyces, have been identified as safe and effective candidates for gut health applications. This review addresses the current understanding of the mechanism of action of probiotics, their functions in human health, and their therapeutic potential for various diseases. We emphasize the importance of prioritizing probiotic administration along with conventional medicinal drugs for their wide benefits and fewer side effects. Our findings aim to direct future studies on the modes of action of probiotics against emerging health challenges.
Introduction
In the early days, a relationship between microorganisms and humans was observed. It is a very interesting fact that humans cannot survive without microorganisms. In the human body, the head to toe is covered with microorganisms, which protect the human body. The gut contains complex, stable, and beneficial microorganisms that help in various ways, such as digestion of food, increasing immunity, and providing many necessary enzymes. Microbiota refers to the various groups of microorganisms, such as bacteria, archaea, eukaryotes, and viruses, that are present under specific conditions. Gut microbiota community composition can be changed due to some factors. In this microbial jungle, a variety of microorganisms (fungi, viruses, bacteria, and even parasites) can inhabit it. It was previously mentioned in the literature, 100 trillion microorganisms reside in the intestine, which is 10 times larger than the cells of the human body [1]. Currently, the good bacteria in the gut have been compromised because of the modern lifestyle, introducing many pathogenic bacteria to the gut, which prevents the beneficial role of good bacteria. It is logical to increase the number of beneficial bacteria to maintain good gut health [2]. Many bacteria help cure diseases by having a symbiotic relationship with the host.
These are referred to as probiotics. Probiotics, defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”, Anjana and Tiwari [3] 2022, have been studied for their ability to promote a balanced and diverse gut microbiome, which is essential for maintaining overall health [1]. If a sufficient amount of these bacteria is ingested, they can confer several health benefits, such as those provided by gram-positive bacteria like Lactobacillus and Bifidobacterium [4]. Overconsumption of antibiotics can disturb gut microbiota functionality, thereby killing beneficial microorganisms. Antibiotics usually fail to differentiate between beneficial and harmful microorganisms. The main reasons for antibiotic resistance are improper use of antibiotics, lack of proper knowledge, and misuse of antibiotics [5, 6].
Frequent use of antibiotics also destroys genital tract bacteria and weakens the immune system. This issue has encouraged researchers to find natural alternatives to restore the good bacteria in the body and treat a variety of gastrointestinal infections [7]. The primary source of gut microbiota is the mother, who transfers the gut microbiome vertically during birth. The composition of the gut microbiota depends on the mother’s flora, genetic factors, and medication use. 97% of the gut bacteria are anaerobic, and the majority of strains found are Bacteroidetes (Porphyromonas, Prevotella, and Bacteroides), Firmicutes (Ruminococcus, Clostridium, Lactobacillus, and Eubacteria), and Actinobacteria (Bifidobacterium) [4, 8–10]. Recent studies have shown that probiotics may help improve immune function, protect against pathogenic bacteria, affect the gut-brain axis, and aid in the adsorption of food and nutrients (Figure 1). In addition, probiotics can play a role in the gut, providing beneficial gut bacteria that create a physical barrier to prevent unwanted bacterial ingestion. Therefore, the benefits of probiotics can be addressed as the prevention of diarrhea, irritable bowel syndrome (IBS), ulcerative colitis, and Crohn’s disease. The gut-brain axis is also interconnected, and many studies have suggested that probiotics may help in the management and regulation of mental disorders. A clinical trial with 86 students found that after treatment with probiotics for 28 days, there were improvements in their behavior, such as panic anxiety, neurophysiological anxiety, worries, and mood regulation. In addition, a clinical study reported that probiotic mixed strains of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 for 8 weeks improved mental health and sleep [11].
To ensure health benefits, a good amount of probiotics in the gut is required with regular food intake. The strains of probiotics should be from human sources and contain a few major features, such as: 1. benefits to the host, 2. survival in the intestine, 3. it is also used as a feed additive to improve the intestinal epithelial cell (IEC) membrane, 4. creation of antibiotic substances against infections, and 5. stabilizes intestinal microflora. The number of probiotics should be large enough to provide a sufficient number of bacteria in the gut [7]. Lactic acid bacteria (LAB) are good sources of probiotics, except for Streptococcus and Enterococcus. In many food products, LAB are widely used without any adverse effects. Probiotics are mostly isolated from the human gut, and it is known that large quantities of probiotic consumption are advised as a functional food; for example, Bifidobacterium can be found 1011 cells/g in the intestine [12, 13]. Probiotics can also increase the metabolism of host tissues, particularly the gastrointestinal mucosa and liver [14]. As research continues to uncover the critical link between gut microbiota and host health, the consumption of probiotics has increased significantly. While much attention has been focused on their beneficial functions, potential risks such as infections and the transfer of antibiotic resistance genes to pathogenic bacteria are often overlooked. Some studies have shown that probiotics may have harmful effects on the host. In case of immunocompromised states, D-lactic acidosis, brain fogginess, bacteraemia, and antibiotic resistance gene transfer could be found [15]. This review offers a comprehensive exploration of mechanistic approaches and contemporary perspectives on the therapeutic benefits of probiotics in disease prevention and treatment.
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Some materials are used for the encapsulation of probiotics.
| Component | Advantage | Disadvantage | Probiotic | Therapeutic effect of strain(s) | Reference |
|---|---|---|---|---|---|
| Proteins | |||||
| Milk proteins (whey protein and/or casein) | Acid-stable; pepsin-resistant; bile salt-resistant; enzyme-activated controlled release in intestine; exceptional film-forming properties | Potential allergen | Lactobacillus rhamnosus GG, Bifidobacterium longum 1941, Lactobacillus delbrueckii ssp. bulgaricus, Streptococcus thermophilus | Preventing diarrhoea, primary rotavirus infection, and atopic dermatitis | [40–42] |
| Plant proteins [zein (corn protein) and/or soy protein] | Enhanced protection due to forming a hydrophobic shell; pH and thermal stability | Might aggregate and compromise stability | Bacillus subtilis 168 | Increasing abundance of beneficial gut bacteria | [43, 44] |
| Gelatin | Improved antioxidant property; mucoadhesion can potentially enhance probiotic delivery | Denatures at high temperatures | Lactobacillus rhamnosus GG Bifidobacterium bifidum Lactobacillus acidophilus Bacillus coagulans Saccharomyces boulardii | Gut disease prevention, such as IBS, IBD, diarrhea prevention. Improving immune modulation, such as allergy, inflammation. Vaginal or urinary tract infection improved by Lactobacillus strain | [45] |
| Albumin (egg white protein) | Gelling and cross-linking ability; specific site-targeting properties | Potential allergen; pH sensitive | Lactobacillus acidophilus TISTR 1338 | Preventing diarrhoea, treating Helicobacter pylori, improving respiratory tract infections, lowering serum cholesterol levels and improving the host’s lactose tolerance levels | [46, 47] |
| Silk fibroin | Resistant to gastric acid and bile acid; resistant to enzymatic action; improved adhesion to IECs | Can be brittle | Lactobacillus plantarum, Enterococcus faecium KCTC 13115BP (EF-3), Streptococcus thermophilus KCTC 14471BP (ST-27), Bifidobacterium animalis subsp. lactis KCTC 13116BP (BL-5), Bifidobacterium bifidum KCTC 13114BP (BB-1), Lactobacillus acidophilus KCTC 13117BP (LA-7) | Reducing diarrhea, inhibiting pathogenic bacteria, reducing blood cholesterol, and improving liver cirrhosis and obesity | [48, 49] |
| Polysaccharides | |||||
| Alginate | High encapsulation efficiency; significant increase in the survival rate of probiotics; cost-effective | Reduced probiotic protection at low pH | Saccharomyces cerevisiae strains, Saccharomyces boulardii, Enterococcus faecium, Bacillus licheniformis, fruit-derived lactic acid bacteria (LAB) | Preventing and treating diarrheal diseases (acute infantile diarrhoea, antibiotic-associated diarrhoea, nosocomial infection); preventing systemic infection; managing IBD; immunomodulation; prevention and treatment of allergies; anticancer effects, treating high cholesterol, and relieving lactose intolerance | [50] |
| Chitosan | The only commercially available water-soluble cationic polymer, quick biodegradation | Reported to have some antimicrobial and antifungal actions; therefore can be used as the shell but not the capsule during encapsulation strategies | Lactobacillus and Bifidobacterium spp. | Boosting host immunity; improving growth of targeted microorganisms; eliminating harmful bacteria | [51] |
| Pectin | Itself a prebiotic, meaning it can be fermented by beneficial bacteria in the gut, further supporting their growth and activity; resistant to enzymatic digestion in the stomach and small intestine | Might modify probiotics’ metabolism | Lactobacillus plantarum | Protection against intestinal epithelial barrier disruption | [52, 53] |
| Carrageenan | Improved probiotic survival in acidic conditions | No significant resistance to bile salts | Lactobacillus plantarum | Enhancing gut health by securing a good number of probiotic bacteria in the GI tract in highly acidic conditions | [54] |
| Gellan and/or xanthan gum | Excellent gelling and malleability properties; biocompatible and biodegradable; heat and acid-stable | May be unstable in physiological conditions | Lactobacillus paracasei 28.4 | Antifungal activity against Candida albicans in the oral cavity | [55, 56] |
| Cellulose | Cheap; can be used to make pH-responsive capsules when complexed with other materials | It can lead to structural defects when used in complexes | Lactobacillus spp., Bifidobacterium spp. | Treatment of severe skin infections and chronic wounds | [57] |
| Starch and/or dextran | Acid-resistant | Can be unstable under thermal stress; can form irregular aggregates | Lactobacillus rhamnosus | Enhancing probiotic stability and viability under simulated gastrointestinal conditions | [58] |
| Pullulan | Itself a potential prebiotic; increased probiotic viability after acid and bile exposure | Can be expensive | Lactobacillus acidophilus NRRL-B 4495 | Preventing and treating gastrointestinal infections and diarrhoea; stimulating immune responses that promote the effects of vaccination or even prevent certain allergic symptoms | [59, 60] |
| Lipids | |||||
| Plant oils (olive, sunflower, soybean, corn) | Improved survival in gastric and pancreatic juices | May interfere with probiotic survivability | Candida adriatica, Candida diddensiae, Nakazawaea molendini-olei, Nakazawaea wickerhamii, Wickerhamomyces anomalus, Yamadazyma terventina | Synthesizing polyunsaturated fatty acids (PUFAs), which provide health benefits | [61] |
| Dioleoylphosphatidic acid and cholesterol | Preserves the native viability and biosafety of naked probiotics | Might induce an inflammatory response | Escherichia coli Nissle 1917 (EcN) | Preventing and treating Salmonella typhimurium (STm) and dextran sulfate sodium (DSS) induced colitis | [62] |
IBD: inflammatory bowel disease; IBS: irritable bowel syndrome; IECs: intestinal epithelial cells.
Alam ST, Rayhan ABH, Ahmed MU, Khan MT, Jame JF, Islam MM, et al. Mechanisms of action and health benefits of probiotics: a comprehensive review. Explor Drug Sci., 2025;3:1008129, https://doi.org/10.37349/eds.2025.1008129
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