Frontier to probiotics: Human-microbiome superorganism

Lilley and Stillwell described the term “probiotics” in 1965, which means “for Life” (Gasbarrini et al. 2016; Talwar 2015). Laconically, the worth of probiotics is that it is an aid for salubrious health when taken in appropriate quantity (Morelli and Capurso 2012; Chouraddi et al. 2023). Elie Metchnikoff proposed that altering the microbiome of the intestines with host-friendly bacteria (Lactobacillus) could have a positive impact on health and postpone dementia. They are potentially involved in improving the chronic inflammation of the intestinal region, atopic dermatitis, diarrheal infections, bowel syndrome, sepsis, vaginitis, mucosal immunomodulation, allergies, and liver disorders (Wallace et al. 2011; Mackowiak 2013; Hati and Prajapati 2022). The human is an exceptional reservoir of a vibrant and heterogeneous group of microbes, which are vital for the host organism. This host-microbial interaction forms a human-microbiota superorganism (Kerry et al. 2018). This microbiota is known as probiotics. They could be bacteria or yeast (Bermudez-Brito et al. 2012; Fredua-Agyeman et al. 2017; Oak and Jha 2019). Prebiotics are specialized feed ingredients that boost the activities and growth of beneficial bacteria in the gastrointestinal tract (GIT) and eliminate the pathogenic ones (Gibson et al. 2017).

Probiotics are being employed in a variety of industries to treat and prevent a wide range of diseases and health issues. The way they are prepared and used for the host’s welfare is improving daily. Recently, a high level of probiotic consumption has become a huge caption about the significance of microbiota in human health and disease management. The industrial global consumption of probiotics will increase to approximately US $70 billion in 2023 (Khoruts et al. 2020). The fundamental criteria for selecting probiotics are adaptability to intestinal conditions, mucosal attachments, and lack of competitiveness (Marco et al. 2017).

Probiotic mechanisms of action

Probiotics have been investigated to modify the intestinal microbiota, reduce the permeability of the intestines, reduce the inflammatory conditions, and affect metabolism (Halloran and Underwood 2019; You et al. 2022). Recent studies have suggested that epithelial hypoxia restricts the amount of oxygen available in the colon, resulting in the preservation of a healthy microbiota that serves as a microbial organ and produces metabolites that support host diets, immune training, and niche security, during homeostasis (Cani 2017; Byndloss and Baumler 2018). However, the correlation between human health and the efficacy of probiotics has been undoubted. And most of the mechanisms behind the useful impact of probiotics on human beings are still undiscovered or multifactorial. Anyhow, the main probiotic mechanisms of action include (1) secretion of antimicrobial substances, (2) pathogen’s competitive exclusion, (3) immune system modulation, (4) adhesion to the intestinal mucosa, and epithelial barrier enhancement (Fig. 1) (Plaza-Diaz et al. 2019).

Fig. 1
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Mode of actions of probiotics

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Probiotics: a potent antimicrobial substance

Probiotic strains produce antimicrobial components such as low-molecular-weight organic acids (lactic acid and acetic acid) and bacteriocins. Antimicrobial substances are capable of causing bacterial death by intracellular pH reduction and dissociating the cytoplasm of pathogens (Bermudez-Brito et al. 2012; Alam et al. 2022). Bacteriocins (produced by lactobacilli and bifidobacteria) are antimicrobial peptides that stop pathogens from multiplying. The growth of multidrug-resistant Shigella spp., helicobacter, Clostridium difficile, rotaviruses, and Escherichia coli could be inhibited through the use of bacteriocins created by Lactobacillus acidophilus and L. plantarum and could also be used against a variety of uropathogens (Kumar et al. 2016; Mokoena 2017). Bacteriocins frequently possess a limited spectrum and are most successful at eliminating bacteria that belong to the bacteriocin generator, leading to steady colonization and invasion inhibition by competing with other species (Halloran and Underwood 2019). Based on their antibacterial properties against Gram-positive bacteria like Listeria, multiple investigations have shown the benefit of bacteriocin-producing probiotic bacteria in food security and preservation (Yang et al. 2014; Iseppi et al. 2021; Lahiri et al. 2022).

Immunomodulatory effects of bacteriocins

Recent investigations have demonstrated the successful migration of bacteriocins such as nisin A, plantaricin 423, and bacST4SA across endothelium and epithelial cells without any harmful effects. They also exhibit stability within the blood plasma (Flynn et al. 2021; Dreyer et al. 2019). These findings provide convincing proof that bacteriocins can pass through the gut-blood barrier, impacting both the local and systemic immune responses (Dicks et al. 2018). Additionally, it is hypothesized that bacteriocins may help to stimulate intestinal epithelial cells (IECs), which in turn create antimicrobial compounds to prevent the colonization of invasive infections (Huang et al. 2021). To reduce inflammation, nisin was discovered to increase the synthesis of anti-inflammatory cytokines while decreasing the production of pro-inflammatory cytokines (Jia et al. 2019).

Studies on the impact of nisin on mice’s immune systems also showed that short-term nisin administration results in a raised in CD4+ and CD8+ T cells, along with a notable decrease in the proportion of B cells. T cells and B cells recover to normal levels after prolonged nisin ingestion, and the number of peripheral blood macrophages/monocytes rises. To exhibit their immune-modulating capabilities in cases of inflammation, bacteriocins often can alter cytokine production via modulating several signaling pathways (e.g., TLR, NF-kB, MAPK) (Huang et al. 2021). According to reports, bacteriocins can activate inflammasomes, which in turn can trigger immune reactions in response to viral infections (Umair et al. 2022).

Pathogen’s competitive exclusion

When one species of bacteria fights more ferociously than other species for receptor areas in the digestive tract, this is termed as competitive exclusion (Bermudez-Brito et al. 2012). These probiotic benefits are mainly unclear in terms of the precise routes and important regulatory systems involved. One of the key processes for the competitive exclusion of pathogens is the decline of luminal pH, competition for nutritional supplies, and formation of bacteriocin or bacteriocin-like compounds (Collado et al. 2010; Soltani et al. 2021; Saha and Saroj 2022). Numerous probiotic metabolites seem to have an impact on how different signaling and metabolic processes in cells are modulated. Elements of probiotics metabolome, including amines, organic acids, bacteriocins, hydrogen peroxide, and others, have been found to react with a variety of receptors in multiple pathways of metabolism that control angiogenesis, inflammation, cellular proliferation, and metastasis (Kumar et al. 2013; Fuhrmann et al. 2022).

Immunomodulatory effects of probiotics

The intestine offers an ideal environment for the development of cooperative interactions between immune cells and commensal microorganisms (Zhang et al. 2019). This complex ecology has developed over time as a result of repeated contact with different antigens. The gut commensal microorganisms are in constant close contact with the cellular and molecular components of gut immunity, modulating immune reactions and assisting in the regulation of gut homeostasis (Mazziotta et al. 2023). Significant health problems, such as cancer, metabolic disorders, chronic inflammation, cardiovascular diseases via the gut-heart axis, and neurological diseases via the gut-brain axis, have all been directly linked to the disruption of this complex microbial population (Martinez et al. 2017; Wang et al. 2019, 2020; Bartolomaeus et al. 2020; Rutsch et al. 2020; Sharma et al. 2021). Moreover, probiotics exhibit potential immunomodulatory effects by interacting with dendritic cells, epithelium, monocytes, and lymphocytes (Taghavi et al. 2017).

Furthermore, probiotic bacteria boost immunity by inducing mucin release, producing several bioactive substances, and competitively excluding pathogens by avoiding their adhesion to the intestinal epithelial surface as well as restricting the growth of pathogens by competing with them for vital nutrients (Raheem et al. 2021; Yesilyurt et al. 2021; Youssef et al. 2021; Yadav et al. 2022; Mazziotta et al. 2023). Probiotics’ immunomodulatory effects differ from person to person and are primarily attributed to the secretion of cytokines and chemokines, TLR activation, or suppression of the nuclear factor-kB cascade (Azad et al. 2018; Bhardwaj et al. 2020; Aghamohammad et al. 2022; Kaur and Ali 2022; Mazziotta et al. 2023). The production of cytokines and antimicrobial peptides by probiotics regulates the JAK/STAT (Janus kinase/signal transducers and activators of transcription) and MAPK (mitogen-activated protein kinase) signaling processes, enhancing the mucosal and systemic immune response (Dinic et al. 2021; Aghamohammad et al. 2022). It is well-known that probiotic surface molecules or fragments of cells can activate the phagocytic ability of macrophages and dendritic cells (Rocha-Ramirez et al. 2017; Liu et al. 2020), thereby helping to increase the cytotoxic activity of NK cells and CD8+ T cells (Aziz and Bonavida 2016; Yousefi et al. 2019; Mao et al. 2020) (Fig. 2).

Fig. 2
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Immunomodulatory role of probiotics 

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Probiotics stimulate the release of cytokines upon adhesion to IECs, activating Tregs, the primary mediators in preserving gut homeostasis (Cristofori et al. 2021; Tripathy et al. 2021; Mazziotta et al. 2023). In the colonic mucosa, Tregs produce more of the anti-inflammatory cytokine, (interleukin-10) than pro-inflammatory cytokines, which may reduce inflammatory reactions and promote immunological tolerance to commensal microorganisms (Cristofori et al. 2021; Tripathy et al. 2021; Mazziotta et al. 2023). To limit allergic reactions and manage autoimmune diseases, probiotics encourage a switch from Th2 to Th1 cells to balance T cell subtypes necessary for gut immunity to operate properly (Cristofori et al. 2021; Yadav et al. 2022). Additionally, the interaction of probiotics with IECs causes maturation of dendritic cells and then induces Tregs, encouraging mature B cells to alter their immunoglobulin type to secretory IgA in Peyer’s patches (Rousseaux et al. 2023). The secretory IgA is crucial for maintaining the strength of the mucosal barrier, inhibiting pathogens from interacting with epithelial receptors as well as neutralizing the toxin produced by bacteria on the mucous membrane (Sakai et al. 2014; Pietrzak et al. 2020).

Probiotics adhesion to intestinal mucosa

The probiotic strains interact with host intestinal mucosa and secrete mucin to prevent the pathogens (Monteagudo-Mera et al. 2019). There are 100 trillion microbes in the intestine’s micro-ecological environment, including bacteria, fungi, viruses, and protozoa. Most of them (99%) are bacteria. The steady and varied gut microbial ecosystem performs complicated metabolic and digestive processes (Lan and Jianqiong 2017). One of the key components of bacterial host interactions that follow bacterial adherence to the host mucosa as an essential requirement is colonization (Dodoo et al. 2017). Various surface proteins of Lactobacillus helped in the formation of mucosal adhesions and a surface bond between the bacteria and the host cell’s mucosal layers. Proteins, polysaccharide substances, and lipoteichoic fatty acids play significant roles in this process (Kotzamanidis et al. 2010; Yu et al. 2022).The surface proteins made by Lactobacillus reuteri that are most extensively studied are known as mucus-binding proteins (Mub) (Desantis et al. 2019). Surface-dependent secretory proteins are essential for mucosal adherence in the Lactobacillus strains (Von Ossowski et al. 2010). Bifidobacterium animalis sub sp. lactis and Bifidobacterium bifdum are also said to have surface proteins that interact with human plasminogen or enterocytes. By destroying cells’ extracellular matrix or enabling intimate interaction with the epithelium, surface proteins contribute to bacterial colonization in the human intestine (Candela et al. 2011). The principal host reaction to pathogenic bacterial invasion is increased production of antimicrobial proteins, including alpha- and beta-defensins, catalysidins, type C lectins, and ribonucleases, that function as the host’s primary means of chemical defense (Gallo and Hooper 2012).

Epithelial barrier enhancement

In humans, the epithelium of the intestine is in direct contact with luminal components and dynamic flora of GIT. Intestinal barrier including the mucous layer, secretory IgA, epithelial junction adhesion complex, and antimicrobial peptides are major defense mechanisms, which are responsible for maintaining epithelial integrity (Ohland et al. 2010; Fatmawati et al. 2020).When these barrier functions are interrupted, bacterial and food antigens can induce an inflammatory response, which leads to intestinal disorders (Sartor 2006; Bron et al. 2017). Through the creation of biofilms, probiotic bacteria can establish long-term residences in the host mucosa, preventing the colonization of pathogens (Halfvarson et al. 2017).

The immune system of the intestinal tract serves as a biological shield that stops immunogenic substances and other harmful germs from penetrating the mucosa and entering the host. This biological barrier, which is created by the release of intestinal immune cells, works in conjunction with the barrier of intestinal epithelial cells to protect against infectious threats (Lan and Jianqiong 2017). Pathogens cannot enter the body because of the physical or biological intestinal barriers. These are made up of the persistent gut epithelium, the layer of mucus, the mucosal immunity, and the intestinal microbiota, which are all interconnected (Iacob et al. 2019). The intestinal epithelium surface acts as a physical barrier that protects against the “outside,” offering a first line of defense against infections. The mucus layer, a hydrated gel that covers the surface of the gastrointestinal mucosa, serves as the second line of defense against invasive pathogenic bacteria and immunogenic components. Mucin produced by goblet cells and antibacterial proteins created by paneth cells makes up the mucus layer. For the gut microbiota, in particular, for bacteria that survive close to the epithelial cells, this provides a protective habitat (Cornick et al. 2015).

Intestinal mucosal immunity, which includes antimicrobial peptides (defensins or lysozymes), gut-associated lymphoid tissues (GALT), mucosal immune cells (such as Th1, Th2, and Treg cells), and secretory immunoglobulin A (sIgA), provides the third layer of defense (Goto et al. 2016; Kurashima and Kiyono 2017). The gut microbiota serves as the body’s fourth line of defense. Through competition, the microbiota keeps pathogens out of the gut mucosa. This process, known as “colonization resistance,” is connected to quorum sensing (QS) (Tytgat et al. 2019). QS (quorum sensing) is crucial for the development of pathogenic and probiotic bacterial biofilms. Additionally, QS components can control cytokine reactions and dysbiosis of the gut as well as preserve intestinal barrier integrity, according to the current investigations as depicted in Fig. 3 (Salman et al. 2023).

Fig. 3
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Enhancement of intestinal membrane barrier due to probiotics

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Probiotics current status

Currently, probiotics gained an excellent interest and becoming a modern era phrase because of the denotation of “for life” and its beneficial effects on host health (Bagchi 2014; Kiousi et al. 2019; Mishra and Acharya 2021). The host gut interactions with intestinal, residential, and temporary microbiota provide a novel field in medical physiology which would shed light on the direct relationship between humans and enteric microbiota (Iacob et al. 2019). Therefore, 76% of physicians believed that probiotics could have a place in their patient management. International Life Sciences Institute (ILSI), an international group of experts, evidenced probiotics functionality in four major areas including chronic intestinal functional disorders, inflammations, metabolism, infections, and various kinds of allergies (Rijkers et al. 2010; Collins et al. 2017).

Probiotic characterization

  1. (i)

    Authentication of the health benefit

  2. (ii)

    Extrapolate to the general human population

This has led to a rejection of most probiotics to date (Shehata and Newmaster 2020, 2021; Kothari et al. 2023).

Demand of probiotics

Probiotics are widely explored and demanded in several fields of applied science, specifically as a nutritional supplement. They are demanded for the treatment against various diseases including diarrhea caused by rotavirus and foodborne allergies. They also influence the prevention and treatment of obesity, varieties of cancer, and infections related to pathogenic microorganisms, which is a thrilling research arena (Kerry et al. 2018). They have also a significant role in the treatment and prevention of constipation, diarrhea, sepsis, chronic intestinal inflammation, irritable atopic dermatitis, vaginitis, bowel syndrome, food allergies, diabetes, and liver disease. They may moderate systemic and immune functioning and boost the functioning of the intestinal barrier and alteration in gut micro-ecology to exert metabolic effects on the host (Wallace et al. 2011; Chang et al. 2019; Kim et al. 2019).

Probiotics: an alternative to antibiotics

Over the long term, in-feed antibiotics (IFAs) were used prophylactically and as a growth promoter in livestock, poultry, and aquaculture around the world to maintain health and production (Yang et al. 2009; Elisashvili et al. 2019). There are several problems with antibiotics; in addition to their side effects, they also destroy normal microbiota of GIT (Vestergaard et al. 2019). The antibiotic treatment of Helicobacter pylori infection leads to a wide range of gastrointestinal side effects including nausea, diarrhea, bloating, vomiting, and cramps in a host (Heta and Robo 2018).

The prohibition on antibiotics uses in animal and poultry feed resulted in reduced productivity (Cheng et al. 2014), because of severe diseases in livestock and foodborne contaminations in consumers (Hao et al. 2014), while antibiotic resistance is another big issue. In this scenario, probiotics could be an alternative to antibiotics and would be warmly welcomed (Al-Khalaifah 2018; Sanders et al. 2018). Probiotics secrete antibacterial substances that can combat harmful bacteria as well as their role in immunomodulation especially mucosal immunity can eradicate pathogens easily (Mazziotta et al. 2023).

Probiotics and disease management

Probiotic strains vary significantly between host species and individuals and also differ according to host genomic makeup, stage, diet components, health status, and previous antibiotics exposure (Henao-Mejia et al. 2013; Tiderencel et al. 2020). Probiotics are being indicated to avoid and enhance the symptoms of allergic diseases like allergic rhinitis and atopic dermatitis (eczema) in infants, as well as gastrointestinal problems like acute, nosocomial, and antibiotic-associated diarrhea, as well as diarrhea caused by Clostridium difficile and some inflammatory bowel diseases in adults (Jakubczyk et al. 2020; Al-Sharaby et al. 2022).

Probiotics have various biomedical applications including potentialized cancer theranostics, antifungal, antiallergic, antiparasitic, antibacterial, antiviral, anti-inflammatory, immunomodulator, and reducer of gastrointestinal disorders (Uccello et al. 2012; Aitoro et al. 2017; Thammasorn et al. 2017). Probiotics in disease management are described in Table 1 and Fig. 4.

Table 1 Disease management through probiotics
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Fig. 4
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Probiotics and disease management

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Probiotics and gastrointestinal tract diseases

Inflammatory bowel disease (IBD) is a chronic disorder that affects the host and intestinal bacteria unfavorably. Patients with IBD have a greater chance of colon and rectal cancer development (Olveira and Gonzalez-Molero 2016). The eating of unhealthy foods high in fat, which changes the microbiota in the human digestive tract, is the main cause of IBD. Using probiotic supplements to restore intestinal microbiota may help patients to avoid interal issues and enhance their overall health (Markowiak and Slizewska 2017). Probiotics with the Lactobacillus plantarum strain have been effective in treating IBD patients. Flatulence is greatly reduced by the Lactobacillus panatarum DSM 9843 strain, while abdominal pain is reduced by the LPO 1 and 299 V strains (Domingo 2017).

Probiotics and lipid metabolism

Cholesterol is a crucial precursor for numerous biochemical reactions that take place within the human body and is crucial for the body’s ability to produce steroid hormones (Schade et al. 2020) while having too much cholesterol in human plasma increases the risk of artery blockage, a major threat to the heart and increased risk of stroke (Ghosh 2012). It has been observed that several probiotic strains, including L. reuteri, Bacillus coagulans, and L. bulgaricus, have hypo choleretic properties. When the patients consumed L. acidophilus L1 milk, a substantial decrease in blood plasma cholesterol levels was observed (Maftei 2019).

Probiotics and chronic wounds

Diabetic patients, fatty people, elderly, and people with persistent burn scars are at risk from non-healing wounds. When given topically, probiotics either cause re-epithelization and collagen synthesis or selectively eliminate pathogenic microbes (which degrade wounds) (Knackstedt et al. 2020). In this context, scientists developed a patch comprising the nitric oxide gas–synthesizing L. fermentum 7230 and evaluated its ability to treat infectious and ischemic rabbit wounds. There was an apparent rise in the formation of collagen and the flow of blood into the injuries (Jones et al. 2012). Antimicrobial probiotic strains have a positive impact on the treatment of chronic wounds. Probiotics that attach to the keratin in this situation displayed antibacterial qualities against Pseudomonas aeruginosa, E. coli, and Propionibacterium acnes. Moreover, similar strains prevented the development of early biofilms In vitro without having an impact on existing biofilms (Lopes et al. 2017). Additionally, strain-specific LGG administration along with skin parasites Staphylococcus hominis and S. epidermidis could be employed to prevent S. aureus colonization (Saeed et al. 2014; Nakatsuji et al. 2017).

Cancer biotherapeutics

Dermatitis, halitosis, urogenital infections, diarrhea, hypercholesterolemia, inflammation, obesity, carcinomas, and irritable bowel syndrome are just a few ailments that could be treated with probiotics. Probiotics particularly have drawn attention because of their capacity to modify cancer signaling (Gorska et al. 2019; Jahanshahi et al. 2020). Notably, probiotics can influence the onset of cancer by inducing apoptosis; metabiotics (capsular polysaccharides, bacteriocins, polyamines, antioxidants, polyphenols, proteins, antimicrobial molecules) are primarily responsible for probiotics’ anticancer effects (Fig. 5) (Singhal and Chaudhary 2021). The term “metabiotics” describes the structural elements of probiotic microorganisms, their metabolites, and signaling molecules with a particular chemical composition which can optimize the physiological processes specific to the host and also regulatory, metabolic, and behavioral responses linked to the activities of the host (Singhal and Chaudhary 2021; Noor et al. 2023).

Fig. 5
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Probiotics role in cancer treatment

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Probiotics in neurological disorders

Around 20% of people globally experience psychological conditions like sadness and nervousness (Bear et al. 2020). A person’s level of well-being can be characterized as having psychologically good health. Psychological studies on rodents typically concentrate on anxiousness, stress, or motivation (Sarkar et al. 2016). Some probiotics known as “psychobiotics,” according to Dinan and associates, are “live microorganisms, which ensure beneficial effects on mental health whenever taken in acceptable doses” (Dinan et al. 2013; Sarkar et al. 2016). To carry out and control neural activities like learning, memory, and mood, as well as other mental processes, psychobiotics synthesize, distribute, and regulate neurotransmitters like glutamate, brain-derived neurotrophic factor (BDNF), serotonin (5-HT), and gamma-aminobutyric acid (GABA) (Cheng et al. 2019).

Microbial disease management: microbes vs microbes

Probiotics work against pathogens, as L. acidophilus therapy is effective against GIT fungal colonization. Lactobacillus plantarum produces specific double-stranded RNA for viral inhibition in penaeid shrimp (Thammasorn et al. 2017). Bacillus sp. improves L. rohita immunity against pathogenic strains, i.e., Aeromonas hydrophila (Nandi et al. 2017). Salmon aquaculture is badly affected by Flavobacterium psychrophilum causing the bacterial cold-water disease. A probiotic strain Oncorhynchus mykiss has a potential against BCWD (Ghosh et al. 2016), while an effective treatment of chronic diarrhea is through lyophilized heat-killed Lactobacillus acidophilus (Remes-Troche et al. 2020).

Foodborne allergies and probiotics

Humans face various food-borne allergies (FA) as mentioned in Fig. 6 (Grimshaw et al. 2014). Neonatal antibiotic treatment reduced gut microbiota diversity and boosted foodborne allergy sensitization (Stefka et al. 2014). It is reported that a different probiotic strain, i.e., Bifidobacterium spp. and Lactobacillus, reduces foodborne allergies (Sharma et al. 2017; Kerry et al. 2018). Lactobacillus rhamnosus has potential against eczema, inflammation, itchiness, redness, and rashes on skin (Wickens et al. 2012). Lactobacillus plantarum is also beneficial in atopic dermatitis treatment (Mitropoulou et al. 2013; Prakoeswa et al. 2017). Lactobacillus decreases the symptoms of allergic rhinitis in children (Lin et al. 2013), while Lactobacillus gasseri has a role in asthma treatment (Chen et al. 2010, 2022).

Fig. 6
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Sources of food-borne allergies

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Antiparasitic activity of probiotics

Probiotics are considered as a control of parasitic infections including intestinal and non-gut infections as presented in Table 2 and provide strain-specific defense counter to parasites through multiple mechanisms (Ajanya et al. 2018). An intestinal pathogen Cryptosporidium found as an oocyst in water causes devastating gastrointestinal disorders by impairing sodium and water absorption which leads to diarrhea in immune-compromised individuals. L. reuteri and L. acidophilus NCFM are potential reducers of oocyst shedding (Travers et al. 2011; Pane and Putignani 2022). Giardia lamblia, an intestinal parasite, is controlled by Lactobacillus johnsonii, Lactobacillus casei MTCC, and Enterococcus faecium SF68 (Shukla et al. 2008). Eimeria is a parasite that causes coccidiosis in chicks, livestock, and other small animals (Madlala et al. 2021). Various probiotic strains including Lactobacillus spp., Pediococcus acidilactici, Saccharomyces boulardii, and Pediococcus acidilactici reduced the Eineria acervuline infection (Lee et al. 2007; Lee et al. 2007; Mohsin et al. 2022).

Table 2 Antiparasitic activity of probiotics
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Probiotics and industrialization

Futuristically, probiotics will act as a mainstay of various industries such as aquaculture, livestock, and poultry (Deng et al. 2022). The disease outbreak is the major restraint for aquaculture production in various countries of the world instead of the utilization of antibiotics and chemical compounds. The non-antibiotic and eco-friendly agents (probiotics) are the key to aquaculture management (De et al. 2014; Jamal et al. 2020). Probiotics are a sustainable, biotic, and feasible strategy to intensify the shrimp industry via disease control and improvement of fish mucosal immunity, mucosal microbiota, and immunomodulation of mucosal surfaces (Lazado and Caipang 2014). Aquaculture is now an emerging and viable source of proteins, vitamins, nutrients, and food safety for humans, chiefly in those regions where livestock is comparatively scarce (De et al. 2014; Azra et al. 2021). The specialized probiotics and prebiotics in the mixture might prove to be the subsequent stage to limit the risk of enteric disorders and microbial diseases of livestock. Probiotics and prebiotics could be utilized as a food additives to modulate animal gut microbiota to recover health (Markowiak and Sliżewska 2018; Quigley 2019).

Safety profile analysis for humans

It has been confirmed from the above literature survey that no certain and obvious negative impacts have yet been reported. Direct administration of the probiotics with the human body organs did not appear toxic yet. Many disease models and trials also confirmed the safe nature of probiotics for disease management (Zommiti et al. 2020). As they do not get absorbed into the cellular pathways, there is no chance of their transfer between different animals or residue formation (FAENA 2005).

Safety profile analysis for animals

Probiotics/microorganisms that have been applied to the feed for animals have not produced any significant demerits globally and, hence, deemed safe for animal use. As the mode of their absorption into the animal body is not well understood, they also have not been proven to interrupt any metabolic activity of the animals. Due to availability of the less knowledge apart from the countless trials on their efficacy, it is impossible to issue a decree on their exact potential (Hughes and Heritage 2002).

Safety profile analysis for the environment

After imparting the beneficial role to the digestive tract, probiotic bacteria partially die due to the competition with the other microbiota and expel rest out of the body as others. These probiotics also digest as the other nutritional components of the food; hence, there is negligible chance of them reaching the manure and even the soil grounds (Dinleyici et al. 2014). Moreover, as all the probiotics are safe, they all are of natural origin, and no serious impact on the environment is expected (Bull et al. 2013).

In a nutshell, further detailed, in-depth, and mechanistic studies are inevitable to evaluate the exact status and impact of the probiotics on the biosphere in the long and short term.

Futuristic prospects

There is a necessity for comprehensive guidelines about the characteristics, effectiveness of probiotics and acceptable daily intake via dietary products. Probiotics might be the novel biotic agent to limit health issues and revolutionary key to various industries such as aquaculture, livestock, and poultry. Since the first review published by Tournut in 1989 regarding probiotic uses in livestock, several types of research have been done on bacteriotherapy in animal husbandry. As every animal has different gut flora even of the same species, with the recent development in DNA technologies, future farmers will be able to send a microflora sample to their animal scientists, who will analyze microbes already in the GIT of animals and suggest, which probiotic addition will maximize the health and growth of the animal.