The most addressed area in the study of probiotics is the gastrointestinal system since they proliferate in it. Therefore, many benefits have been demonstrated. For this section, a total of 68 articles showed different uses for the gastrointestinal tract when administrated B. licheniformis, mainly findings on microbiota modulation, followed by approaches to gastrointestinal benefits in livestock animals and finally in specific diseases such as enteritis, colitis, diarrhea, etc. One of the most relevant studies showed that in combination with B. subtilis could achieve an increased villus height in the ileum and a decrease in the crypt depth in the jejunum as well as the ratio of both, which can improve nutrient absorption and general digestion (Wang et al., 2021). Another study using the same combination of probiotics found that they secrete the enzymes protease, lactase, lipase, and amylase, which also provide benefits in digestion (Yang et al., 2021). Moreover, working individually with the diversity of the microbiota, an increase in Lactobacillus and Firmicutes was obtained (Chen and Yu, 2020). Also when induced colitis in rats, it lowered parameters of inflammation, weight loss, severity, and colon shortening (Li et al., 2019).

From the revised study models, the various types of studies focus on birds, mainly broilers, principally hens, and chickens, followed by those derived from pigs and marine animals, and finally rodents. Therefore, we can visualize that current gastrointestinal studies of B. licheniformis are more focused on the benefits for farm animals, and they seek to avoid the consumption of antibiotics by replacing them with probiotics. However, with the results on inflammation and gut microbiota regulation, it should be considered in further studies like irritable bowel disease, constipation, and colorectal diseases in animal models and humans.

Probiotics have already been proven to enhance the absorption of some nutrients (calcium, zinc, and vitamin B12) and lower the incidence of anemia, which may help children grow by preventing infections and micronutrient shortages. Previous research has explored the effects of probiotics on the diet in terms of weight and height gain in malnourished children, as well as the possibility of weight gain in well-nourished children in underdeveloped nations (Onubi et al., 2015). It has been proposed that supplementing locally accessible foods with probiotics could be a useful intervention for improving child growth, particularly in underdeveloped nations (Onubi et al., 2015).

However, for the specific application of B. licheniformis in animals and growth, a total of 55 studies were found, being one of the most relevant uses for this probiotic. Our study observed that most animal publications reported positive results on growth, mass gain, and feed conversion against weight gain. These publications also show that the number of viable units of B. licheniformis and its markers are associated with overall homeostasis. It was found that supplementing broilers with this probiotic significantly improved their weight and gain (Rodrigues et al., 2020), as well as their average daily feed intake. The growth was also associated with B. licheniformis competitive growth against pathogens (Chen and Yu, 2020). In lambs, the supplementation shows a significantly low feed efficiency (dry matter intake/average daily gain) (Jia et al., 2018). Also, results from a study on the pathogenicity of GFP-tagged Vibrio parahaemolyticus Dahv2 and the protective impact of the probiotic strain, Bacillus licheniformis Dahb1, on Asian catfish indicated that these organisms could be employed to manage aquatic illnesses and benefit the aquaculture sector (Gobi et al., 2016). This can potentially contribute to improving not only the health and fitness of animals intended for human consumption but also to human studies and child growth.

Regarding the close relationship that the immune system and its inflammatory process have with the digestive system, a total of 44 studies for immune response parameters and trials were found and 27 studies had different inflammatory markers on different models. Current information showed that in combination with B. subtilis, a slight increase in IL-10 can be obtained, a decrease in TNF-α, and a protective effect when exposed to a specific antigen (Deng et al., 2017). Also, it has been reported that the intake of B. licheniformis is related to a reduction of pro-inflammatory cytokine IL-8 and an increase in of IgM and, IgG (Sun et al., 2021), while IgA antibodies, and higher concentrations of total serum proteins and globulins was also found (Gong et al., 2018). In a report about the challenge of the pathogen E. coli and in combination with B. subtilis in pigs, the authors found upregulation in the expression of TLR4, NOD2, iNOS, IL-8, and IL-22, CCL28 chemokines and its CCR10 receptor mRNA genes, and an increase of subpopulations of CD4-CD8- T-cells and no changes in the number of IL-7Rα-expressing cells (Yang et al., 2016). A specific summary of the most relevant articles on the anti-inflammatory effect of Bacillus licheniformis is shown in Table 2. In the aquaculture field, the enhancement of immunity is frequently mentioned as a reason why probiotics employed in the fishery are efficient at mediating protection against pathogenic diseases. Long-term feeding could maintain the persistent activation of immune cells throughout the feeding time. An application of BL probiotics was successful in sustaining systemic and mucosal immunity, as well as resistance to A. hydrophila (Gobi et al., 2018).

When compiling the data, it was observed that the deepest and most available studies on mediators and effectors related to the immune system are found in mice and broilers, but there are still many areas of the immune system associated with this probiotic pending to be explored, since its participation on multiple metabolic pathways could aid on immune-related diseases and disorders, principally the ones related to reported inflammatory mediators.

Scientific research has centered on studying pathogenic microorganisms and developing methods to prevent and treat human illnesses for many years. Conversely, in a symbiotic connection, other bacterial species may benefit the host. Antibiotics are not only the most common method used to treat infections currently (Silva et al., 2020) but also it may affect commensal bacteria in the host. Antibiotic overuse could have negative consequences both for patients and public health, such as drug-specific adverse effects and the selection of multidrug-resistant microorganisms. Probiotic formulations with immunostimulatory effects or inter-bacterial competition between beneficial and harmful bacteria are among the many that claim to benefit human health. Probiotics have been suggested as a novel and viable technique for controlling and preventing a variety of infectious diseases in this specific topic (Yang et al., 2020). For this probiotic, a current research found that B. licheniformis produces proticin, an antibiotic of phosphorus-containing triene (Todorov et al., 2022).

For the antimicrobial results in B. licheniformis, a total of 27 studies demonstrated its potential effect. In aquaculture, a study on zebrafish (Danio rerio) challenged the potential probiotic Bacillus licheniformis protective effects and in vitro antagonistic activities against GFP-tagged Vibrio parahaemolyticus. Zebrafish infected with it had 100% death, but zebrafish treated with B. licheniformis experienced total survival after 30 days (Girija et al., 2018). Also, in combination with B. Breve, an in vitro study showed significant inhibition against the adhesion of the pathogenic K. rhizophila (Rohith and Halami, 2021) and anti-vibrio activity (Sekar et al., 2019). The crude extract reveals antiviral activities against porcine epidemic diarrhea virus in Vero cells, and lower the viral shedding in piglets (Peng et al., 2019), Also in piglets, the sodium butyrate generated by B. licheniformis improves Salmonella shedding (Barba-Vidal et al., 2017). Other studies show that this probiotic has antimicrobial proteins, and high auto- and co-aggregation capabilities against pathogenic bacteria (Pahumunto et al., 2021). In the biomedical fields, the biosynthesis of silver nanoparticles employing the probiotic Bacillus licheniformis may be applied to manage bacterial populations that create biofilms (Shanthi et al., 2016). Multiple studies show that intestinal eubiosis is attributable to the inhibition of pathogenic microorganisms, so the aforementioned factors can achieve a reduction in infections. Although most of the studies focus on animals, multiple studies show that probiotics from the Bacillus family have antimicrobial properties also in humans and therefore comparable results can be expected (Hallaj-Nezhadi et al., 2022). Despite the promise advantages of probiotics for intestinal health, there is still no agreement or standardization on delivery techniques or the use of probiotic dosage forms for antimicrobial therapy; however, B. licheniformis, because of its potential effect as an antimicrobial agent and its survival through the gastrointestinal tract, could be a novel strain for the research of it.

Oxygen species, mainly referred to as free radicals, and oxidative stress are a matter of concern nowadays. Recent studies have reported that antioxidants are produced by probiotic strains that scavenge hydroxyl radicals and superoxide anions. Molecular pathways of diabetes, atherosclerosis, inflammatory bowel disease (IBD), and damage to the heart, brain, or transplanted organs have all been linked to oxidative stress. The most acceptable species and strains for a probiotic antioxidative intervention for a certain clinical condition must be carefully considered (Hoffmann et al., 2019).

For the specific results of B. licheniformis, 27 studies revealed its potential effect. In a study with fish, it was shown that in combination with B. subtilis, they improved the levels of glutathione s-transferase (GST), glutathione reductase (GR) (Salehi et al., 2022), and combined decrease in the T-BARS marker was obtained, which indicates an increase in antioxidant enzymes (Guardiola et al., 2017). This probiotic alone had a positive impact on antioxidant capacity in the liver, serum, and intestine in birds (Zhao et al., 2020). Another study revealed that dietary supplementation with B. Licheniformis Dahb1 could improve innate immune function by reducing the oxidative stress linked to ammonia accumulation in tissues and blood (Gopi et al., 2022). The study for specific probiotic strains that give the most effective prevention and mitigation of oxidative stress must be continued to produce novel products with the potential to prevent oxidative stress. Further research is required to fully understand the antioxidative capabilities of prospective probiotics. Although most of the studies focus on animals, multiple studies show that probiotics from the Bacillus family have antioxidant properties also in humans and therefore comparable results can be expected.

Metabolic disorders can encompass a set of diseases that lead to different routes and mechanisms that affect many vital organs; that is why for purposes of this review we have specifically limited the metabolic section to diabetes and obesity, since other parts could address gastrointestinal, hepatic, cardiovascular, and neurological problems and are deepened on the other sections or have not been studied yet. Gut microbiome regulation and probiotic beneficial metabolic effects have been investigated in patients with type 2 diabetes mellitus. Probiotics have lower total cholesterol, triglyceride levels, CRP, inflammatory biomarkers, glucose, insulin, and blood pressure regulation. Also, they have shown an improvement in HDL levels without affecting BMI or LDL levels (Kocsis et al., 2020).

Table 3 summarizes the most relevant articles on this topic. A total of 23 studies revealed the potential effect of B. licheniformis, alone or in combination with other probiotics or prebiotics in parameters related to diabetes and obesity, such as glucose levels, lipidic profiles, etc. Some of the mechanisms involved with Bacillus licheniformis are activating the AMPK pathway and suppressing the NF-κB (Lu et al., 2021). These effects specifically for B. licheniformis and its potential role as a supplementary therapeutic method were demonstrated in mice with a high-fat diet induced, since they showed a reduction in body weight, while it improved glucose tolerance, obesity, and insulin resistance (Cao G. T. et al., 2019). Also in high-fat diet rats, a reduction in total cholesterol, triglyceride, LDL levels, and body weight gain was observed at the same time that strains linked to obesity were reduced in microbiota composition (Li et al., 2020). Finally in humans, a 12-week trial of BL in combination with other spore-forming bacilli probiotics showed significant triglyceride reduction in patients with hypertriglyceridemia (Campbell et al., 2020). Further studies on long-term administration need to be done to complement the effect on this type of metabolic disease.

The gut–liver axis in most liver diseases has been proved, from the simple pathogenesis of fatty liver diseases (both alcoholic and non-alcoholic) to liver failure and, finally cirrhosis (Wiest et al., 2017). In Bacillus licheniformis specifically, a total of 13 studies showed its potential effect to prevent liver damage. Some of the results include the modulation of the expression of genes linked to fatty acid production and oxidation in the liver (Zhao et al., 2020), prevention of mild fibrosis and piecemeal necrosis in the liver (Wang et al., 2020), acute liver toxicity induced with acetaminophen, one of the most used analgesics and antipyretic agents in the world (Neag et al., 2020), reduction of liver weight, hepatic steatosis and effective alleviation of liver inflammation, possibly by modulating the NF-κB signaling pathway (Lu et al., 2021), and many others.

In the most relevant articles, BL interaction with gut bacteria showed a positive influence on liver damage, and a study on sheep and lambs has resulted in a significant decrease in serum levels of total bilirubin and cholesterol, parameters that point out a boost in transference from liver to bile, and leading indirectly to an improvement in liver function (Devyatkin et al., 2021). Also, the interaction of B. flexus and B. licheniformis showed a reduction in serum cholesterol, and improve in HDL-cholesterol, respectively, along with other biochemical parameters and microbiota studies that indirectly validate its efficacy and propose its use for human consumption (Shobharani et al., 2019). Another study revealed the role of BL in the homeostasis of gut microbiota and the modulation of bile acid; and in combination with Lactobacillus salivarius and Pediococcus pentosaceus, it prevented liver fibrosis and downregulated the hepatic expression of profibrogenic genes in rats (Shi et al., 2017). These results demonstrate one of the most relevant applications of B. licheniformis and could lead to novel applications in human hepatic diseases, both alcoholic and non-alcoholic.

The microbiota in humans has been recognized as a new prospective risk factor for cardiovascular diseases. Atherosclerosis, heart failure risks, and influence of the gut microbiota in them have been previously reported. Even though animal research has revealed that gut microorganisms may influence heart disease risk, no such relation has been observed in humans (Forkosh and Ilan, 2019). For the case of Bacillus licheniformis, even though animal studies have not reported benefits on specific cardiovascular diseases yet, results obtained in eight studies demonstrate that not only significant improvement in hematological parameters, in general, could be achieved in combination with other Bacillus species (Adorian et al., 2019) but also regulation of other disorders that indirectly could be related to cardiocirculatory problems, such as triglycerides regulation (Campbell et al., 2020) for atherosclerosis, and its role in risk reduction of heart attacks, coronary diseases, cardiopathies, and many other heart illnesses (Peng et al., 2017). Also in humans, a study of 30-day probiotic supplementation of BL with other oral spore-based could reduce dietary endotoxemia (McFarlin et al., 2017). Even though endotoxemia is the result of a translocation of LPS into the circulation, studies revealed its link to an elevated risk of many cardiovascular diseases (Moludi et al., 2020).

Another application in heart failure prevention could be Bacillus licheniformis potential role in microbiota regulation. A recent study linked microcirculatory abnormalities in heart failure patients with anatomical and functional alterations in the gut. Emerging data suggest that gut bacteria may play a role in the pathogenesis of heart failure (Kamo et al., 2017). The breach in the intestinal epithelial barrier might allow microbial compounds to enter the bloodstream, exacerbating this disease by triggering inflammatory responses, an effect this probiotic has previously been reported to prevent in many articles and further elaborated upon. When looking for up-to-date information on cardiovascular disease, it is important to focus on the microbiota as a pathway for treatment of heart failure and other diseases. Additional research is necessary; however, the notion of the heart–gut axis might pave the way for advances in the development of novel diagnostics and therapy techniques focused on cardiovascular health.

The gastrointestinal physiology, including digestion and gut bacteria composition, is influenced by abnormal brain activities. The gut microbiota has a strong robust bidirectional interaction with the central nervous system and impacts its outcome and mechanism of it. According to several neurological findings on the gut–brain axis, this enhances gut homeostasis. The mechanisms underlying this axis are diverse, with multiple routes involved both directly and indirectly (Suganya and Koo, 2020). Probiotic supplementation as an aid for biochemical signaling of the microbiota–gut–brain pathway, in which the intestinal microbiota, enteric nervous system, and central nervous system get connected, could have a positive influence against dysbiosis and enhancement of neuroactive substances such as serotonin or dopamine. New terms such as psychobiotics, also known as live biotherapeutics or substances with bacterially mediated beneficial effects on the brain, are currently being studied as a single or combination therapy for psychiatric and neurodevelopmental disorders, as well as possibly neurodegenerative diseases, as they could become novel treatment alternatives toward the prevention and control of brain disorders (Long-Smith et al., 2020).

Although it was found that only two studies for the specific application of B. licheniformis in neurological effects (apart from the psychological mentioned later), this could be mainly because of the recent attention given to this field. A 28-day trial in weaning piglets showed beneficial effects of neurotransmitters in serum and hypothalamus, serum γ-aminobutyric acid, and higher colonic concentrations of butyrate and valerate in combined probiotic supplementation (BL, B. subtilis, and Clostridium butyricum) in comparison with control and antibiotic-treated groups (Cao G. et al., 2019). An application in humans in the neurological field involved pediatric central system tumor’s side effects study caused by radiotherapy including mouth ulcer, nausea, vomiting, abdominal pain, and diarrhea. Although the effect of BL preparation on children’s survival rates and tumor recurrence was not evaluated in this investigation, it showed an improvement in intestinal function and repairment, inflammatory responses, and immunity that could lead to a better efficacy in the final treatment (Du et al., 2018). These results encourage to improve further investigations of this probiotic in neurological diseases, such as Alzheimer’s, Parkinson’s, multiple and amyotrophic lateral sclerosis, etc.

Probiotics have been used recently in investigations to assist in negative emotions, altered behaviors, cognitive performance, and stress relief. Many scientific investigations are underway to see if probiotic supplements might assist those who are suffering from psychological stress. For Bacillus licheniformis, a total of two studies were found, one focused on aquaculture and the other on rats. For the purpose of this review, psychological disorders have been separated from the rest of neurological diseases to delve deeper into them.

The first one revealed that in combination with B. Amyloliquefaciens, results showed an improvement in larval fish survival and transport stress resistance (Tarnecki et al., 2019). One of the primary goals of any aqua farmer or entrepreneur seeking to maximize output is to reduce stress on farmed fish. This major challenge in aquaculture has prompted extensive research on reducing or eliminating the impact of stress on cultivated animals. Among the several stress reduction treatments used in aquaculture, dietary probiotic interventions have emerged as promising, empirical, and long-term solution (Ciji and Akhtar, 2021).

The second one, which focused on B. licheniformis alone exhibited, an improvement in behavioral changes, nervous system metabolites, neurotransmitters, and gut microbiota changes in the rat model, and demonstrated a possible new mechanism of subhealth status alleviation in psychology and behaviors, specifically because of the gut microbiome that could consume more propionic acid, resulting in alterations in brain neurotransmitters as glutamic acid (Glu), γ-aminobutyric acid (GABA), and 5-hydroxytryptophan (5-HT). At the same time, it could contribute to the reduction of norepinephrine in the brain, corticosterone, and TNF-α in the blood, as well as the inhibition of hyperactivity on the hypothalamic–pituitary–adrenal (HPA) axis and lead to anxiety reduction (Feng et al., 2022). These investigations provide new possibilities for further research on emotional disorders, their pathogenesis, and the development of their therapeutic approaches in animals and humans.

Periodontal healthcare and oral cavity mechanisms seem to be far from the application of probiotics interaction with the host; however, some of the topics mentioned before such as the stimulation of immune responses, inhibition of pathogens in the gastrointestinal tract, and synthesis of antimicrobial compounds could aid on the prevention and treatment of dental care diseases. In the context of disease pathogenesis, the microbiological relationship between these two mucosal locations may be linked. Several studies have found that oral bacteria can travel to the gastrointestinal tract via hematogenous and enteral axis (Kitamoto et al., 2020). It has been postulated that an oral–gut communication axis exists, but its role in the development of neurodegenerative illnesses has yet to be discovered. However, the use of probiotics for the control of various oral health disorders, like dental caries, periodontitis, gingivitis, halitosis, burning mouth syndrome, and oral cancer has been previously studied on many probiotic strains (Mishra et al., 2020). For Bacillus licheniformis and dental care, only one study has been reported focused on periodontitis.

Periodontitis has been linked in a lot of research to other chronic non-communicable diseases such as cardiovascular and neurological diseases (Sansores-España et al., 2021). Both deepened the beneficial effect that B. licheniformis has on them. In this specific study, the combined effect of BL with B. subtillis in rats with an experimental periodontitis-induced model was done. The main results showed a reduction in alveolar bone loss and the number of peripheral blood eosinophils in probiotic therapy concluding that with this study, further research on human clinical trials could be applied (Messora et al., 2016). This study opens new perspectives of B. licheniformis potential effect, not only on the whole oral healthcare applications mentioned before but also on the ones related to bone-loss diseases such as osteoporosis, a disease which has also been suggested to be approached with probiotics (Collins et al., 2018).