Bacteria from the Bacillus spp. family have been a subject of numerous scientific research studies and clinical trials around the world for their probiotic and medicinal properties. Several samples of such studies are featured below for your information.

Bacillus subtilis
Bacillus subtilis is a widespread microorganism in nature and a GRAS (Generally Recognized As Safe) substance. B. subtilis can grow fficiently in low-cost carbon and nitrogen sources (Olmos and Paniagua- Michel, 2014). Some B. subtilis strains demonstrated their potential as dominant species by isolation in GI tracts, secretion of quorum-sensing entapeptide, competence, and sporulation factor (Sorokulova,2013). Commercial B. subtilis strains include Bio-Kult_ (Protexin Health Care), Biosporin_ (Biofarma, Ukraine); Garars (Russia), Lactipan Plus (Instituto Biochimico Italiano SpA, Italy), Bibactyl (Tendiphar Corporation, Vietnam), Biosubtyl DL (IVAC, Vietnam), Bidisubtilis (Bidiphar Binh Dinh Pharmaceutical and Medical Equipment Company, Vietnam), and Biobaby _ (Ildong Pharmaceutical Co. Ltd., Korea)

Probiotic B. subtilis strains have been investigated for having antimicrobial, antiviral, and anticancer effects. B. subtilis strains have been used as single and mixed type commercial probiotics. B. subtilis P223 inhibits the adhesion of Salmonella enteritidis, Listeria monocytogenes, and E. coli to the HT-29 cells (Jeon et al., 2017). Bacillus subtilis 3 can produce antibiotics including amicoumacin A and nonamicoumacin against H. pylori (Pinchuk et al.,2001).

A B. subtilis recombinant strain exhibited antiviral activity against influenza virus, herpes virus, and equine encephalomyelitis virus in in vitro and experimental animal models, respectively (Chudnovskaya et al., 1995). Bacillus subtilis 3 demonstrated an antiviral effect in animal models and against their antiviral substances owing to the expression of peptide P18 (Starosila et al., 2017). The probiotic B. subtilis 3 and peptide P18 together demonstrated their antiviral effect against the influenza virusA/FM/1/47 (H1N1) in Madin-Darby canine kidney (MDCK) cells and mice at a concentration of 106 CFU/well and 107 CFU/mouse, respectively. In mice, the lethal rate decreased to 30% for 14 days while the control, without B. subtilis 3, died on day 8. The probiotic B. subtilis ATCC 6051 was reported to have c-aminobutyric acid (GABA) producing ability (Wang et al., 2019). GABA has many well-known functions including anxiety inhibition, sleep promotion, reducing blood pressure, and enhancement of immune response (Sarkar et al., 2016).

Bacillus strains as human probiotics: characterization, safety, microbiome, and probiotic carrier

Na-Kyoung Lee • Won-Suck Kim • Hyun-Dong Paik

Food Sci Biotechnol (2019) 28(5):1297–1305



Background: Bacillus probiotics health benefits have been until now quite poorly studied in the elderly population. This study aimed to assess the effects of Bacillus subtilis CU1 consumption on immune stimulation and resistance to common infectious disease (CID) episodes in healthy free-living seniors.

Results: One hundred subjects aged 60–74 were included in this randomized, double-blind, placebo-controlled, parallel-arms study. Subjects consumed either the placebo or the probiotic (2.109 B. subtilis CU1 spores daily) by short periodical courses of 10 days intermittently, alternating 18-day course of break. This scheme was repeated 4 times during the study. Symptoms of gastrointestinal and upper/lower respiratory tract infections were recorded daily by the subjects throughout the study (4 months). Blood, saliva and stool samples were collected in a predefined subset of the first forty-four subjects enrolled in the study. B. subtilis CU1 supplementation did not statistically significantly decrease the mean number of days of reported CID symptoms over the 4-month of study (probiotic group: 5.1 (7.0) d, placebo group: 6.6 (7.3) d, P = 0.2015). However, in the subset of forty-four randomized subjects providing biological samples, we showed that consumption of B. subtilis CU1 significantly increased fecal and salivary secretory IgA concentrations compared to the placebo. A post-hoc analysis on this subset showed a decreased frequency of respiratory infections in the probiotc group compared to the placebo group.

Conclusion: Taken together, our study provides evidence that B. subtilis CU1 supplementation during the winter period may be a safe effective way to stimulate immune responses in elderly subjects.

Probiotic strain Bacillus subtilis CU1 stimulates immune system of
elderly during common infectious disease period: a randomized, double-
blind placebo-controlled study.

Marie Lefevre1*, Silvia M. Racedo2, Gabrielle Ripert2, Béatrice Housez3, Murielle Cazaubiel3, Corinne Maudet3, Peter Jüsten1, Philippe Marteau4 and Maria C. Urdaci2

Lefevre et al. Immunity & Ageing (2015) 12:24 DOI 10.1186/s12979-015-0051-y

Efficacy of Bacillus spp.

As probiotic has been screened in several in vitro and in vivo animal models and a few have also been validated in human clinical trials. The available data from these studies has presented the beneficial effects of different strains of Bacillus spp. for human health. For example, several researchers have recognized the preventive role of Bacillus probiotic in gut physiology impairment conditions (Lopetuso et al., 2016; Zhang et al., 2016). The amelioration of dysbiosis and gut inflammation by probiotic Bacillus strains was established by the ability of balancing gut flora toward beneficial microbial population and associated anti-inflammatory agents which helped to recover intestinal mucosa from illness generated injuries. Recently, an in vivo study by Haldar and Gandhi (2016) revealed that the oral administration of skim milk containing Bacillus coagulans B37 and Bacillus pumilus B9 decrease coliform counts in feces of treatment groups. Besides, the beneficial effect of B. coagulans on the gut metabolism is also evaluated by Lee et al. (2016), who reported that feeding of B. coagulans along with soya pulp to cholic acid fed rats, suppressed the production of secondary bile acid, improved intestinal permeability and reduced the bactericidal effect of bile acid which supported the growth of beneficial microbiota into the intestine.
The positive effect of Bacillus spp. to distant cells, beyond GIT has also been established by several researchers. In this context, Foligné et al. (2012) studied the effect of probiotic Bacillus subtilis PB6 on cytokine release profile of human immunocompetent peripheral blood mononuclear cells (PBMC). Strain PB6 induced substantial levels of IL-10 but very low levels of IL-12, TNFa, and IFNg on human PBMC. In an interesting study, Abhari et al. (2016) demonstrated that oral administration of B. coagulans and inulin combination could improve the biochemical and clinical parameters of rheumatoid arthritis in rat model.
Besides having direct effect over host health, strains of Bacillus are currently also being employed for protective and therapeutic effect against several systemic clinical syndromes particularly, metabolic disorders. Several studies have established that natural products involving Bacillus spp. can be an alternate, safe and cost effective therapy for the management of metabolic syndromes. In one such study, solid state fermentation of soybean with B. amyloliquefaciens resulted in production of 1- Deoxynojirimycin, a potent alpha-glucosidase inhibitor (Cai et al., 2017). On similar lines, 13 weeks of dietary intervention with B. licheniformis 67 fermented soybean paste significantly prevented obesity related parameters in diet induced obese C57BL/6J mice (Choi et al., 2016). Fermented soybean fed group displayed lower values for blood glucose, insulin, serum and hepatic lipid profile, and body weight compared with high fat diet control group. The anti-obesity activity was attributed to the production of poly gamma glutamic acid by selective strains. The anti-diabetic functionality of B. licheniformis fermented soybean had also been attributed to the reduced accumulation of beta amyloid in brain hippocampus, preventing beta amyloid mediated insulin resistance and beta cell death. The study displayed glucose homeostaisis effects of fermented soybean in diabetic rats with experimental Alzheimer’s type dementia (Yang H.J. et al., 2014). Similarly, Purified exopolysaccharide from B. subtilis suppressed cardiovascular disease related parameters in streptozoticin induced diabetic rats (Ghoneim et al., 2016). In this study, the therapeutic effect of EPS was recorded due to reduced blood glucose, troponin, total serum cholesterol, LDL, and VLDL as well as suppression of ICAM and VCAM expression. Earlier, Zouari et al. (2015) also explored the anti-diabetic and antilipidemic properties of biosurfactant produced by B. subtilis SPB1 strain in alloxan induced diabetic rats. Upon oral administration, the biosurfactant reduced the plasma alpha-amylase activity and rendered protection to pancreatic beta cells. Besides displaying hyperglycemic effects, biosurfactant administration regulated serum lipid profile by promoting HDL-cholesterol and delaying the absorption of LDL-cholesterol and triglycerides. Aforesaid studies clearly support the rich bio-therapeutic potential of spore forming Bacillus strains…

Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives

Fouad M. F. Elshaghabee, Namita Rokana, Rohini D. Gulhane, Chetan Sharma and Harsh Panwar

FRONTIERS IN MICROBIOLOGY REVIEW published: 10 August 2017 doi: