Supernatant Synbiotic

SUPERNATANT SYNBIOTIC FORMULA

BioImmersion’s Probiotic Super Blend is an advanced formulation of naturally occurring whole probiotic organisms with their Supernatant metabolites and Oligoribonucleotides (ORNs or MicroRNA). 30 billion CFU per gram.*

The super blend includes: Probiotics-Bifidobacterium longum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus, Streptococcus thermophilus; Prebiotics- Inulin from Chicory root; Supernatant [or postbiotic]- a nutritional metabolites “soup” that is created from each of the probiotic organisms, which include their lactic acid, enzymes, vitamins, short-chain fatty acids, bacteriocins, bio-surfactants, bile salt hydrolase, and their ORNs (Oligoribonucleotides; microRNA). The supernatant is freeze-dried along with the good bacteria to form a powerful antimicrobial formula.*

Short chain fatty acids are also known to be the main nutritive energy source for the enterocytes (cells of the intestinal lining), hence, increasing production of short chain fatty acids improves the overall integrity of the GI tract membrane and tightening up cell junctions.*

Our probiotics are naturally occurring, whole organisms with their microRNAs (what ORNs are made of), they wake up quickly and are ready to multiply and build a robust healthy ecosystem in our alimentary canal, from mouth to anus. In order for probiotic to multiply, they need particular foods: dietary fiber and prebiotics they can metabolized in the GI Tract. Inulin, polyphenols, and beta glucan have been found to be excellent sources of fiber and prebiotic for microbes to ferment and metabolize (Holscher & Holscher et al., 2017; 2015, Etxeberria et al., 2013). The Supernatant Synbiotic formula is Vegan, Kosher, Non GMO, and free of Dairy, Soy, and Gluten.*

Supernatant Synbiotic Formula was developed to address the mounting problem of life-threatening hospital generated infections (nosocomal infections) from organisms such as C. difficele, Staph aureus, Klebseilla, and vancomycin-resistant Enterococcus faecium. The formula is comprised of supernatant’s many nutrients including the well-researched antibacterial substances such as bacteriocins, which suppress the growth of pathogenic bacteria (Cotter & Hill, 2013). Probiotics and their supernatant’s metabolites, including microRNA (or ORNs) are shown in research to regulate a balanced ecosystem in the GI tract and protect against bacterial pathogens (Aguilar et al., 2019; Chenoll et al., 2017; Goldenberg et al., 2013; Górska et al., 2016; Kawahara et al., 2015).*

A synbiotic: Synbiotic is defined as a “mixture of a prebiotic and a probiotic that beneficially affects the host by enhancing the survival and the implantation of live microbial dietary supplements in the gut, by selectively stimulating growth and/or activating the metabolism of a specific or few number of health-promoting bacteria” (Gibson & Roberfroid, 1995; Roberfroid, 2002). Most of BioImmersion’s probiotics formulas are synbiotics, which means they include prebiotics from plant fibers and inulin from chicory root. Inulin is naturally found in many different plant foods, such as garlic, onions, asparagus, chicory, artichokes, bananas, and more (Gibson et al., 1994; 2010).*

The Microbiome Project has taught us thathuman microbiota, the microorganisms that live inside us (GI Tract, mouth, vagina) and on us (skin), consist of trillion symbiotic microbes (Ursell et al., 2012). First coined as “microbiome” by Joshua Lederberg in 2001, microbiome is the combined genes of the microbiota, and signifies “the ecological community of commensal, symbiotic, and pathogenic microorganism that literally share our body space and have been all but ignored as determinants of health and disease.” In other words, the microbial communities. Rob Knight emphasizes that there are10 trillion human cells to 100 trillion microbial cells (2017, TED talk) – which means, there are more of ‘them’ than of ‘us.’ Aptly, Turnbaugh et al. (2012) describes this amazing genome collective of human and ‘other’ as a human “supra-organism.”

Supra-Organism:  How do we achieve harmony and health as a human supra-organism? Just like plants rely on their microbiome for life-support functions (e.g., nutrients acquisition and protection against stressors and pathogens), so do humans rely on their microbiome for better health (Pérez-Jaramillo et al., 2018). Since each person embodies a unique system of human genes as well as harbors a “core set of specific bacterial taxa” (Qin et al., 2010), researchers are coming to the conclusion that plant-based foods healthily build our body cells and contribute the right nutrients and fiber to our core microbiota. In essence, researchers of traditional tribes find that the ‘hunter-gather’ still eats more plant-based diet, high in fiber, and very low animal meat, while the Western or modern societies eat protein and meat intensive diets (Caprara, 2018; Desmond et al., 2018; Gomez et al., 2016; Obregon-Tito et al., 2015; Schnorr et al., 2016, 2014; Turnbaugh et al., 2009; Ley et al., 2006).

Hence, achieving a healthy ‘supra-organism’ requires a combination of plant-based foods that nourishes and healthily feed both micro-organisms and human beings -- precisely the principles that BioImmersion employ in the super blend and other formulations. To quickly form healthy colonies, organisms must have the type of foods they need – plant fiber and polyphenols. Food & microbial science show a special interactive relationship between polyphenols from plant-foods and probiotics–a ‘two-way relationship between polyphenols ←→ microbiotia,’ each helps the other, and together they modulate the gut microbiota to benefit human health (Cardona et al., 2013; Pathak et al., 2018).

MICROBIAL ECOLOGY

History:  Probiotics are transient organisms found in a variety of fermented foods, from grains, to fruits, vegetables, legumes like soy, and dairy. Historically, these foods were consumed daily in every part of the world. Probiotic microorganisms belong mostly to the following genera: Lactobacillus, Bifidobacterium, and Lactococus, Streptococcus, Enterococcus (Markowiak & Śliżewska, 2017).

In 1965, Lilly & Stillwell defined the meaning of probiotics as substances produced by protozoan which stimulated another organism, in opposition to antibiotic which inhibits or kills other organisms. Parker (1974) later defined probiotics as ‘organisms and substances which contribute to intestinal microbial balance,’ while Savage (1977) described the microbial ecology of the gastrointestinal tract as “10¹⁴ [100 trillion] indigenous prokaryotic and eukaryotic microbial cells” (p. 107). Microbial organisms were further described by Fuller (1989; 1992) as a supplemental food, ‘live microbial feed supplement’ that effect the host (animal or human) by improving intestinal microbial ecology and balance.  The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations defined probiotics as “live microorganisms which when administered in adequate amount confer a health benefits on the host” (2001; see also Tufarelli & laudadio, 2016).

In October 2013, the International Scientific Association gathered an expert panel to redefine and discuss probiotics. The agreement that probiotics confer health benefits was reinforced, and a more accurate wording was used to describe probiotics as, “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” (Hill et al., 2014). In this way, the panel differentiated between probiotics as microorganisms and the commensals that are natural in the gut microbiota. However, when these commensal strains are collected from the gut, isolated, and characterized as giving health benefits, they can then be referred to as probiotics. In other words, probiotics need to show they are effective. Unfortunately, the term probiotic is used to sell skin care, shampoos and all sorts of other products, without the due diligence that signify the effectiveness of the probiotic, and therefore, misleading the public. To use the term ‘probiotic’ – a health effect must be shown (Hill et al., 2014).

Lactic acid bacterial (LAB): LAB species typically produce lactic acid as a main end-product of carbohydrate and fiber fermentation. LAB organisms are known for their adhesion to the mucus layer of the GI tract. This mucus layer plays an important role in protecting the intestinal epithelial cells against pathogens and damage, as well as provide a perfect milieu for LAB organisms to attach, grow and form their communities (Nishiyama et al., 2016). Streptococcus thermophilus is not part of the Lactobacillus species although this microorganism is also considered a lactic acid bacterium (Kechagia et al., 2012). Bifidobacterium uses a different metabolic pathway, and its name is actually a ‘misnomer’ as very few Bifidobacterium adopt a bifid morphology (even when exposed to stressful conditions), while the rod structure is the intrinsic morphology of the majority (Rajashekharan et al., 2017).

Beneficial Microbiota Milieu:  Probiotic organisms have the potential to shift the gut microbiota milieu (composition) from a pathogenic predominance to a more beneficial micro-biotic ecosystem (Costello et al., 2012; Schnorr et al., 2016; Zitvogel et al., 2017). The fermentation process by probiotics in the gut microbiota keep at bay harmful pathogens by preventing their growth (Anzaku & Pedro, 2017). They assist the body’s immune system and contribute to a host of other positive health benefits. When the balance in the microbiome shifts toward a pathogenic community, it weakens the abilities of the helpful microbiota communities. An impaired microbiome is repeatedly shown in research to lead into conditions such as obesity, inflammatory bowel diseases, and other chronic illnesses (Patil et al., 2012; Schnorr et al., 2016; Kobyliak et al., 2016).

An important conversation in the scientific community is the role probiotic play in creating or modifying the composition of the gut microbiota toward better health (Sanders et al., 2018; Bron et al., 2017; Sanders, 2016). Globally, obesity is progressing and almost at the level of a pandemic, causing other chronic metabolic diseases to manifest (Dahiya et al., 2017). Since probiotics are transient in nature, and the gut lining continues to shed and renew its cells, how long do probiotic microbes stay in the gastrointestinal tract? And does a shorter duration have a power to create a healthy microbiome? Some say that although probiotics may not reside in the gut longer than two weeks, they do offer many benefits (Sanders et al., 2018), while others see a need for more specific research on fecal microbiota and probiotics (Kristensen et al., 2016).

At the core of this discussion is the need for a unified global regulatory frameworks and research methods, including a universal classification (nomenclature) of probiotic organisms to decrease consumer confusion and improve the scientific requirement for the commercial industry at large (Sanders et al., 2011). The gut microbial community includes bacteria (anaerobic and aerobic), viruses, fungi, with a variety of disease-causing pathogens and parasites (Howarth & Wang, 2013). Some microorganisms are shown to be helpful for human health, while others cause much distress. We have discussed how our diet, in particular, heavy consumption of meat, eggs, and dairy, change the composition of the microbiome (Matthews et al., 2018; Singh et al., 2017), but moreover, exposure to pesticides and herbicides (Stanaway et al., 2017), and other foods and environmental chemicals (Roca-Saavedra et al., 2017), create a heavy burden on the body’s ability to function well. As research continues to uncover new facets of research on micro-organisms, including probiotics, we will update this document. Stay tune also to Seann Bardell’s Forward Thinking emails found in the News within the Resources tab: http://blog.bioimmersion.com.

What do probiotic achieve in our GI Tract? Although the gut microbiome is a complex ecosystem of microorganisms, probiotics have exhibited many health benefits, including weight loss and improvement of metabolic diseases (Dahiya et al., 2017), boosting and supporting the immune system (de Vos et al., 2017), strengthening the intestinal barrier function (Blackwood et al., 2017), supporting colicky babies (Rhoads et al., 2018; Pärtty et al., 2012), and of course competing against pathogenic bacteria (Szajewska et al., 2016; Ayala et al., 2014; Johnston et al., 2012; Manzoni et al., 2006).

Even more so, probiotic organisms perform multitudes of other beneficial functions in the body: research shows that probiotics help to lower toxins (Yu et al., 2016; Qixiao et al., 2015; Amalaradjou & Bhunia, 2012), keep cholesterol down (Cani et al., 2011, 2009), assist in weight management (Everard & Cani, 2013), digestion and absorption of nutrients (Wang & Ji, 2018; Francavilla et al., 2017), elimination (Eskesen et al., 2015; Dimidi et al., 2014), and even function as anti-aging mediators (Buford, 2017; Nagpal et al., 2018). In other words, probiotics are shown in research to maintain a healthy ecological balance in the human gut and perform many beneficial functions.

SUPERNATAT

What is supernatant?   Supernatant is the fermented medium created during the culturing process of probiotics. Supernatant is the fermented “soup” that contains important probiotic metabolites, such as enzymes, peptides, proteins, vitamins, short chain fatty acids, and other nutrients and factors, including antimicrobials such as Bacteriocins that may be used as a possible alternative to antibiotics (Cotter, Ross, & Hill, 2013; Yang et al., 2014). Supernatant, or as some call it, “postbiotic” (Auilar-Toalá et al., 2018), or “parabiotic” (Choudhury & Kamilya, 2018), is shown in research to have powerful antimicrobial properties with the potential to block adhesion, invasion and translocation of E. coli, yet it is gentle enough to be used to ‘enhance neonatal resistance to systemic Escherichia coli K1 infection by accelerating development of intestinal defense’ (He et al., 2017). In fact, Lazar et al.’s (2009) in vitro study concluded that the soluble probiotic metabolites, or supernatant, might actually interfere with the beginning stages of adherence and colonization of selected E. coli. This means that the supernatant itself exudes protective effects (Lazar et al., 2009), as well as work synergistically with probiotic organisms to stimulate the immune system against pathogenic invasion (Ditu et al., 2014).

Immunobiotics:  The combination of lactic acid bacteria (LAB) and their metabolites is given much consideration as a method to improve human immune response against viral and fungal overgrowth. The term “immunobiotic” is a relatively new way to describe the antimicrobial qualities exerted by probiotics and their metabolites (Arena et al., 2018). The term ‘immunobiotic’ has been proposed to define beneficial microbes with the ability to regulate the immune system and lower inflammation of the gut tissue (Villena & Kitazawa, 2017; Villena et al., 2016). For example, the probiotics L. rhamnosus and L. plantarum carry immunobiotic properties and are shown to increase protection against viral intestinal infections (Albarracin et al., 2017). In a different study on mice, Kikuchi et al. (2014) discovered that oral administration of L. plantarum enhanced IgA secretion in both intestine and lung tissues, supporting against influenza virus infection. Immunobiotics, the combination of probiotics and their supernatant metabolites, have been found to support and benefit respiratory immunity (Zelaya et al., 2016), modulate mucosal cytokine profiles, IgA levels, and more, in various conditions of gastrointestinal inflammation (Carvalho et al., 2017).

Bacteriocins and Antimicrobial Properties:  One of the properties that is given much attention is the bacterially produced antimicrobial peptides of bacteriocins (e.g., Cotter & Hill, 2013; Yang et al., 2014; Cotter et al., 2005). Already in 2005, Cotter & Hill observed that bacteriocin nisin functions by binding to lipid II, which is also the target of vancomycin antibiotic. This led to the suggestion that ‘bacteriocin nisin’ could be used as a template to design novel drugs. In 2018, the research to discover the mechanism of bacteriocin against pathogenic activity, including Staphylococcus aureus, continued with the discovery of critical features in the structure of bacteriocins that gives it such a ‘potent activity against pathogenic staphylococci’ (O’Connor et al., 2018).

Metabolic Disorders:  Intestinal dysbiosis and endotoxemia have been linked to metabolic disorders: obesity, insulin resistance, and type 2 diabetes (Leite et al., 2017). Bacterial lipopolysaccharides (LPS) is a molecular element of the outer membrane of Gram-negative bacteria, and typically consist of lipid A (or endotoxin), a ‘core’ oligosaccharide, and a distal polysaccharide, (or O-antigen). LPS also are found in diverse Gram-negative bacteria, many of which are pathogenic to both humans and plants (Raetz & Whitfield, 2002). LPS (also termed endotoxin) serves as a shield from the environment and at the same time is recognized by the immune system as a marker for the entrance (or invasion) of pathogens, which in turn causes inflammatory response, and in an extreme response can bring about endotoxic shock (Rosenfeld & Shai, 2006).  LPS causes inflammatory immunogens that circulate at low grade levels in healthy individuals, while high continuous levels instigate pro-inflammatory markers in the blood, e.g., interleukin-6, interleukin-1-alpha, interferon-gamma, triglycerides and post-prandial insulin. Proinflammatory markers are correlated with the risk of developing a variety of chronic illness, including increase risk of atherosclerosis (Erridge et al., 2007; see Cani et al., 2007).

Since the body is a mechanism of many interactive systems and components, a reaction in one system can instigate a positive or a negative chain of events in another. For example, in a clinical study, Leite et al. (2017) demonstrated that Gram-negative species (e.g., Bacteroides vulgatus and rodentium) were found in stools of individuals with type 2 diabetes, as well as an increase of pro-inflammatory interleukin-6 (IL-6) in their plasma. In other words, gut dysbiosis and metabolic endotoxemia have been linked to metabolic disorders, such as obesity, diabetes, and insulin resistance (van Olden et al., 2015). The gut microbiota contributes to many processes in the human host’s body, and the host provides a place of residence for the survival of the microorganisms (Leite et al., 2017). This give and take relationship has to be delicately balanced.

Epigenetic Changes: Bhat et al. (2017) considers dietary metabolites that are derived from the gut microbiotic population as critical modulators of epigenetic changes in both animals and humans.  Nutrients in the gut are produced by microbial metabolisms of fiber, which means that short-chain fatty acids, polyamines, polyphenols, vitamins, and other metabolites, participate in “various epigenomic mechanisms that reprogram the genome by altering the transcriptional machinery of a cell in response to environmental stimuli” (Bhat et al., 2017). In other words, what we eat does modulate our gut which in turn can influence our health through modulations of genes.

Potent Immune Boosting Nutrients: Adding the natural supernatant metabolic ‘soup’ of potent nutrients that probiotic organisms create while they grow and multiply is showing great potential for human health. Immunobiotics is a study field that endeavors to understand how microorganisms and their supernatant interact with the immune system to support a healthy functioning body (e.g., Górska et al., 2016). Studies on probiotics and their supernatant metabolites are ongoing and add much to our understanding of Turnbaugh et al. (2012) “supra-organism” description of our bodies as an amazing genome collective of human cells and ‘other’ cells.

Continue to learn what supernatant and probiotics do by reading articles in the Research tab.

microRNA or ORNs (Oligoribonucleotides)

History:  Probiotics have had a long history in helping farmed animals combat gut disfunctions caused by overuse of antibiotics to stimulate faster growth. In the 1950s the readily available antibiotics gave rise to the concern that using it as a substance to promote growth was creating resistant populations of bacteria, which means that antibiotics would lose effectiveness against infections from bacteria. Although in 1969 antibiotics were restricted as a growth promotor, the use has not subsided until very recently with the rise of organic and grass-fed animal farms. Fuller (1989) noted that antibiotics have a long-lasting upsetting effect in the gut because of the imbalance caused in the indigenous gut flora. In today’s language, antibiotics disrupt the natural microbiome, causing various diseases (Langdon et al., 2016). Probiotics offer a practical solution as an alternative therapy. For example, they exert antimicrobial properties by inhibiting adhesion of pathogens to the mucosa (Salas-Jara et al., 2016; Chenoll et al., 2011), or produce bacteriocins lethal to the pathogens, as we have seen above in the supernatant section (Reid & Burton, 2002)

MicroRNA Immune-Modulating: Bacteria release immune-modulating molecules when entering the mouth, such as ribonucleic acid or RNA, as though they are ready to defend themselves. Small pieces of RNA, called MicroRNA (miRNA) or oligoribonucleotides (ORNs), are released by pathogenic bacteria as well as a beneficial bacterium such as Lactobacillus casei, which we find in fermented foods like yogurts. Other lactobacillus organism occurs naturally in fruits and vegetables. Marshall (2010) tested L. Casei among other beneficial probiotics to assess their readiness to fight pathogenic organisms in case of invasion and found that these small pieces of RNA or ORNs control the expression of growth genes in the pathogen’s genomes. The bacteria grow faster after releasing the ORNs, mounting a better defense system to invading bacterial infections (Marshall, 2014).

MicroRNA (or ORNs) play important regulatory role in physiological processes in animals (and plants), and is studied for miRNA-based therapeutics (Wahid et al., 2010). miRNA regulate gene expression in all aspects of biology, with certain endogenous miRNAs participating in antiviral defense mechanisms, such as miR-32 with inhibitory effects against the retrovirus type 1 (PFV-1; similar to human immunodeficiency virus such as Epstein-Barr and others) and protects human cells from PFV-1 (Lecellier et al., 2005). Other studies, such as Ma et al. (2011) found another miRNA (miR-29) controlling innate and adaptive immune response to intracellular bacterial infection. With dysbiosis of the gut, inflammation hasten immunological imbalances, influencing the onset of many chronic illnesses, including cancer. The opposite is also a viable solution – maintaining the health of the microbiome (Cianci et al., 2019).

Lactobacillus acidophillus and Bifidobacterium bifidum regulate and modulate the GI-tract, increasing production of certain microRNA that improve colon cancer treatment (Heydari et al., 2018). From the GI-tract to the brain, Zhao et al. (2019) have shown that probiotics protect against inflammatory neurodegeneration caused by neurotoxins in the gut, contributing to a healthier brain function. Probiotics with their supernatant and microRNA or ORNs regulate and support a balanced function of the GI-tract. MicroRNA have emerged as major players in the interaction between host (human body) and bacterial pathogens, with an integral part in the host immune response to bacterial infection (Aguilar et al., 2019; Sunkavali et al., 2017).

Read more on supernatant, chronic illnesses and the science of healthy longevity in our No 7 Systemic Booster: The New Longevity, Here.

PREBIOTIC & FIBER

Definition:  “A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host well-being and health” (Tufarelli & Laudadio, 2016; Gibson et al., 2017; 2014; Macfarlane et al., 2006). A prebiotic is a fiber that resists digestion in the upper bowel and ferments easily in the colon by probiotic organisms. Prebiotic fibers are imperative for the survival and success of microorganisms, without adequate amounts of prebiotic fiber, probiotic cannot successfully grow and replicate in the gut (Holscher, 2016). To positively modulate the composition and ecosystem of the gut, fiber, both plant fibers and prebiotic fibers that are designated as ‘prebiotic’ are a must have daily nutritional food (David et al., 2014).

History:  In 1995, Gibson & Roberfroid introduced the concept of prebiotic as a useful non-digestible fiber such as oligosaccharides, and in particular, fructo-oligosaccharides. In 2017, the International Scientific Association for Probiotics and Prebiotics (ISAPP) released a consensus statement on the definition of scope of prebiotics: The realization that prebiotic fibers stimulate probiotic bacteria’s growth and ability to replicate successfully, and in turn, a healthy community of probiotics modulates the colon’s microbiota by positively changing the ecosystem balance in the GI Tract (Gibson et al., 2017).

Prebiotic Criteria:  Following this consensus, three criteria are required for a prebiotic: 1. That the fiber resists digestion by host (fibers that humans cannot digest in the stomach, such as inulin), 2. that the fiber can be fermented by intestinal microorganisms, and 3. The fibers can stimulate the growth and activity of intestinal bacteria associated with health and well-being (Gibson et al., 2017, p. 492). In other words, adding inulin or other non-digestible fibers to a probiotic formula makes sense. Not only do the fibers help selective organisms grow, a prebiotic also must ‘evoke a net health benefit’ (p. 493). Prebiotics, in fact, activates the bacteria in the gut and improve ‘distant sites’ in the body, such as effecting bone strength, supporting neural and cognitive processes, immune function, skin and more (Collins & Reid, 2016).

Food for Microbes:  Human beings cannot digest most complex carbohydrates and plant polysaccharides, but microbes do – they metabolize the polysaccharides into short-chain fatty acids (SCFAs), including butyrate (Holscher, 2017). Delcour et al. (2016) examine the metabolites (or supernatant) formed by digesting the fiber and concluded that prebiotic increases production of SCFAs is a viable link between prebiotic, probiotics and health benefit. SCFAs are shown in research to regulate glucose metabolism and control body weight (Canfora et al., 2015), produce anti-inflammatory properties to calm inflammatory bowel disease (Tedelind et al., 2007; Vinolo et al., 2011).

Studies show that when we combine prebiotics with probiotics, many other health benefits follow, such as, prevention of insulin resistance, prevention of obesity, and reduction of FPG (fasting plasma glucose) and plasma insulin (Beserra et al., 2015; Cerdó et al., 2019; Razmpoosh et al, 2019, respectively), all markers for cardiovascular, diabetes, and weight management and control.

Other substances that regulate gastrointestinal health are the oligosaccharides in human milk, important in the development of the newborn intestinal microbiota, metabolic, and immunological systems, all important for health later in life. Similar to the oligosaccharides in human milk, short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides have been found to effect early microbiota and increase Bifidobacterium growth, and reduces inflammation in the bowel and skin of babies and the young (Oozeer et al., 2013; Wopereis et al., 2018), reduce weight and inflammatory markers in both young and older individuals (Sahlitin et al., 2019; Fernandes et al., 2017, respectively), and generally contribute to healthy ageing (Tihonen, 2010; Buford, 2017).

Not all dietary fibers are characterized as prebiotics, however, they do contribute positive health effects. For example, microbes are unable to ferment cellulose well, but cellulose increases gut transit time. Psyllium is non-fermentable, yet it is shown to improve glycemic control and reduce cholesterol. Fibers, whether prebiotic or not, are healthy for human health.

 Read more on fiber in the description tab of Be Regular, and see the bibliography in the Research tab.

References

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Aguilar-Toalá, J. E., Garcia-Varela, R., Garcia, H. S., Mata-Haro, V., González-Córdova, A. F., Vallejo-Cordoba, B., & Hernández-Mendoza, A. (2018). Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology, 75, 105-114. Abstract

Albarracin, L., Kobayashi, H., Iida, H., Sato, N., Nochi, T., Aso, H., ... & Villena, J. (2017). Transcriptomic analysis of the innate antiviral immune response in porcine intestinal epithelial cells: influence of immunobiotic lactobacilli. Frontiers in immunology, 8, 57. Article

Amalaradjou, M.A., & Bhunia, A.K. (2012). Modern approaches in probiotics research to control foodborne pathogens. Adv. Food Nutr. Res, 67, 185–239. https://doi.org/10.1016/B978-0-12-394598-3.00005-8

Anzaku, A. A., & Pedro, A. (2017). Antimicrobial Effect of Probiotic Lactobacilli on Candida Spp. Isolated from Oral Thrush of AIDS Defining Ill Patients. J Prob Health, 5(171), 2. Article

Arena, M. P., Capozzi, V., Russo, P., Drider, D., Spano, G., & Fiocco, D. (2018). Immunobiosis and probiosis: antimicrobial activity of lactic acid bacteria with a focus on their antiviral and antifungal properties. Applied microbiology and biotechnology, 102(23), 9949-9958. Abstract

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FOOD SCIENCE: THE APPLICATION AND USE OF PROBIOTICS WITH THEIR SUPERNATANT AND ORNS: L. ACIDOPHILUSB. LONGUM, L. CASEI, L. BULGARICUS, STEPTOCOCCUS THERMOPHILUS, WITH INULIN PREBIOTIC FIBER.

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Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012). Host-gut microbiota metabolic interactions. Science, 1223813. Abstract

O’Connor, P. M., O’Shea, E. F., Cotter, P. D., Hill, C., & Ross, R. P. (2018). The potency of the broad spectrum bacteriocin, bactofencin A, against staphylococci is highly dependent on primary structure, N-terminal charge and disulphide formation. Scientific reports, 8(1), 11833. Article

Sánchez, B., Delgado, S., Blanco‐Míguez, A., Lourenço, A., Gueimonde, M., & Margolles, A. (2017). Probiotics, gut microbiota, and their influence on host health and disease. Molecular nutrition & food research, 61(1), 1600240. Article

Stecher, B. (2015). The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. In Metabolism and Bacterial Pathogenesis (pp. 297-320). American Society of Microbiology. Chapter14

Sun, L., Ma, L., Ma, Y., Zhang, F., Zhao, C., & Nie, Y. (2018). Insights into the role of gut microbiota in obesity: pathogenesis, mechanisms, and therapeutic perspectives. Protein & cell, 9(5), 397-403. Article

Villena, J., & Kitazawa, H. (2017). immunobiotics—interactions of Beneficial Microbes with the immune System. Frontiers in immunology, 8, 1580. Article

Villena, J., Vizoso-Pinto, M. G., & Kitazawa, H. (2016). Intestinal innate antiviral immunity and immunobiotics: beneficial effects against rotavirus infection. Frontiers in immunology, 7, 563. Article

Woo, V., & Alenghat, T. (2017). Host–microbiota interactions: epigenomic regulation. Current opinion in immunology, 44, 52-60. Abstract

Yang, C. M., Cao, G. T., Ferket, P. R., Liu, T. T., Zhou, L., Zhang, L., ... & Chen, A. G. (2012). Effects of probiotic, Clostridium butyricum, on growth performance, immune function, and cecal microflora in broiler chickens. Poultry Science, 91(9), 2121-2129. Article

Yang, S. C., Lin, C. H., Sung, C. T., & Fang, J. Y. (2014). Antibacterial activities of bacteriocins: application in foods and pharmaceuticals. Frontiers in microbiology, 5, 241. Article

Post Antibiotic Care: Antimicrobial & Calming Properties 

Alvarez-Sieiro, P., Montalbán-López, M., Mu, D., & Kuipers, O. P. (2016). Bacteriocins of lactic acid bacteria: extending the family. Applied microbiology and biotechnology, 100(7), 2939-2951. Abstract

Amalaradjou, M.A., & Bhunia, A.K. (2012). Modern approaches in probiotics research to control foodborne pathogens. Adv. Food Nutr. Res, 67, 185–239. https://doi.org/10.1016/B978-0-12-394598-3.00005-8

Anzaku, A. A., & Pedro, A. (2017). Antimicrobial Effect of Probiotic Lactobacilli on Candida Spp. Isolated from Oral Thrush of AIDS Defining Ill Patients. J Prob Health, 5(171), 2. Article

Arena, M. P., Capozzi, V., Russo, P., Drider, D., Spano, G., & Fiocco, D. (2018). Immunobiosis and probiosis: antimicrobial activity of lactic acid bacteria with a focus on their antiviral and antifungal properties. Applied microbiology and biotechnology, 102(23), 9949-9958. Abstract

Ayala, G., Escobedo-Hinojosa, W. I., de la Cruz-Herrera, C. F., & Romero, I. (2014). Exploring alternative treatments for Helicobacter pylori infection. World journal of gastroenterology: WJG, 20(6), 1450. Article

Bermudez-Brito, M., Plaza-Díaz, J., Muñoz-Quezada, S., Gómez-Llorente, C., & Gil, A. (2012). Probiotic mechanisms of action. Annals of Nutrition and Metabolism, 61(2), 160-174. Article

Blaabjerg, S., Artzi, D. M., & Aabenhus, R. (2017). Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients—A Systematic Review and Meta-Analysis. Antibiotics, 6(4), 21. Article

Buford, T. W. (2017). (Dis) Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome, 5(1), 80. https://doi.org/10.1186/s40168-017-0296-0

Chenoll, E., Casinos, B., Bataller, E., Astals, P., Echevarría, J., Iglesias, J. R., ... & Genovés, S. (2011). Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Applied and environmental microbiology, 77(4), 1335-1343. Abstract

Cotter, P. D., Ross, R. P., & Hill, C. (2013). Bacteriocins—a viable alternative to antibiotics?. Nature Reviews Microbiology, 11(2), 95. Abstract

Cotter, P. D., Hill, C., & Ross, R. P. (2005). Food microbiology: bacteriocins: developing innate immunity for food. Nature Reviews Microbiology, 3(10), 777. Abstract

Goldenberg, J. Z., Ma, S. S., Saxton, J. D., Martzen, M. R., Vandvik, P. O., Thorlund, K., ... & Johnston, B. C. (2013). Probiotics for the prevention of Clostridium difficile‐associated diarrhea in adults and children. Cochrane Database of Systematic Reviews, (5). Abstract

Johnston, B. C., Goldenberg, J. Z., Vandvik, P. O., Sun, X., & Guyatt, G. H. (2011). Probiotics for the prevention of pediatric antibiotic‐associated diarrhea. Cochrane Database of Systematic Reviews, (11). Abstract

Junjua, M., Kechaou, N., Chain, F., Awussi, A. A., Roussel, Y., Perrin, C., ... & Chatel, J. M. (2016). A large scale in vitro screening of Streptococcus thermophilus strains revealed strains with a high anti-inflammatory potential. LWT-Food Science and Technology, 70, 78-87. https://doi.org/10.1016/j.lwt.2016.02.006

Manzoni, P., Mostert, M., Leonessa, M. L., Priolo, C., Farina, D., Monetti, C., ... & Gomirato, G. (2006). Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clinical infectious diseases, 42(12), 1735-1742. Article

O’Connor, P. M., O’Shea, E. F., Cotter, P. D., Hill, C., & Ross, R. P. (2018). The potency of the broad spectrum bacteriocin, bactofencin A, against staphylococci is highly dependent on primary structure, N-terminal charge and disulphide formation. Scientific reports, 8(1), 11833. Article

Patel, A., Shah, N., & Prajapati, J. B. (2014). Clinical application of probiotics in the treatment of Helicobacter pylori infection—a brief review. Journal of Microbiology, Immunology and Infection, 47(5), 429-437. Article

Parker, R. B. (1974). Probiotics, the other half of the antibiotic story. Anim Nutr Health, 29, 4-8.

Plaza-Diaz, J., Ruiz-Ojeda, F. J., Gil-Campos, M., & Gil, A. (2019). Mechanisms of action of probiotics. Advances in Nutrition, 10(suppl_1), S49-S66. Abstract

Reid, G., & Burton, J. (2002). Use of Lactobacillus to prevent infection by pathogenic bacteria. Microbes and infection, 4(3), 319-324. https://doi.org/10.1016/S1286-4579(02)01544-7

Rhoads, J. M., Collins, J., Fatheree, N. Y., Hashmi, S. S., Taylor, C. M., Luo, M., ... & Liu, Y. (2018). Infant Colic Represents Gut Inflammation and Dysbiosis. The Journal of pediatrics. https://doi.org/10.1016/j.jpeds.2018.07.042

Szajewska, H., Konarska, Z., & Kołodziej, M. (2016). Probiotic bacterial and fungal strains: claims with evidence. Digestive Diseases, 34(3), 251-259. https://doi.org/10.1159/000443359

Todorov, S. D., de Melo Franco, B. D. G., & Tagg, J. R. (2019). Bacteriocins of Gram-positive bacteria having activity spectra extending beyond closely-related species. Beneficial microbes, 1-14. Abstract

Vanderpool, C., Yan, F., & Polk, B. D. (2008). Mechanisms of probiotic action: implications for therapeutic applications in inflammatory bowel diseases. Inflammatory bowel diseases, 14(11), 1585-1596. https://doi.org/10.1002/ibd.20525

Yang, S. C., Lin, C. H., Sung, C. T., & Fang, J. Y. (2014). Antibacterial activities of bacteriocins: application in foods and pharmaceuticals. Frontiers in microbiology, 5, 241. Article

Yang, C. M., Cao, G. T., Ferket, P. R., Liu, T. T., Zhou, L., Zhang, L., ... & Chen, A. G. (2012). Effects of probiotic, Clostridium butyricum, on growth performance, immune function, and cecal microflora in broiler chickens. Poultry Science, 91(9), 2121-2129. Article

Yin, X., Lee, B., Zaragoza, J., & Marco, M. L. (2017). Dietary perturbations alter the ecological significance of ingested Lactobacillus plantarum in the digestive tract. Scientific reports, 7(1), 7267. Article

Zelaya, H., Alvarez, S., Kitazawa, H., & Villena, J. (2016). Respiratory antiviral immunity and immunobiotics: beneficial effects on inflammation-coagulation interaction during influenza virus infection. Frontiers in immunology, 7, 633. Article

Immune Support

AFRC, R. F. (1989). Probiotics in man and animals. Journal of applied bacteriology, 66(5), 365-378. https://doi.org/10.1111/j.1365-2672.1989.tb05105.x

Aguilar, C., Mano, M., & Eulalio, A. (2018). MicroRNAs at the Host–Bacteria Interface: Host Defense or Bacterial Offense. Trends in microbiology. Abstract

Azcarate-Peril, M.A., Sikes, M., Bruno-Barcena, J.M. (2011). The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol, 301, G401-G424. doi:10.1152/ajpgi.00110.2011.

Bocci V. (1992). The neglected organ: Bacterial flora has a crucial immunostimulatory role. Perspectives in Biology and Medince, 35(2), 251–260. Abstract

Cianci, R., Franza, L., Schinzari, G., Rossi, E., Ianiro, G., Tortora, G., ... & Cammarota, G. (2019). The Interplay between Immunity and Microbiota at Intestinal Immunological Niche: The Case of Cancer. International journal of molecular sciences, 20(3), 501. Abstract

Dargahi, N., Johnson, J., Donkor, O., Vasiljevic, T., & Apostolopoulos, V. (2018). Immunomodulatory effects of Streptococcus thermophilus on U937 monocyte cell cultures. Journal of Functional Foods, 49, 241-249. https://doi.org/10.1016/j.jff.2018.08.038

Galdeano, C. M., Cazorla, S. I., Dumit, J. M. L., Vélez, E., & Perdigón, G. (2019). Beneficial Effects of Probiotic Consumption on the Immune System. Annals of Nutrition and Metabolism, 74(2), 115-124. Abstract

Gern, J.E. (2015). Promising candidates for allergy prevention. Journal of Allergy and Clinical Immunology, 136 (1), 23–28. Abstract

Harata, G., He, F., Takahashi, K., Hosono, A., Miyazawa, K., Yoda, K., ... & Kaminogawa, S. (2016). Human Lactobacillus strains from the intestine can suppress IgE-mediated degranulation of rat basophilic leukaemia (RBL-2H3) cells. Microorganisms, 4(4), 40. doi:10.3390/microorganisms4040040

Lecellier, C. H., Dunoyer, P., Arar, K., Lehmann-Che, J., Eyquem, S., Himber, C., ... & Voinnet, O. (2005). A cellular microRNA mediates antiviral defense in human cells. Science, 308(5721), 557-560. Article

Lilly, D. M., & Stillwell, R. H. (1965). Probiotics: growth-promoting factors produced by microorganisms. Science, 147(3659), 747-748. https://doi.org/10.1126/science.147.3659.747

Ma, F., Xu, S., Liu, X., Zhang, Q., Xu, X., Liu, M., ... & Cao, X. (2011). The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ. Nature immunology, 12(9), 861. Abstract

Madsen, K. (2006). Probiotics and the immune response. J Clin Gastroenterol, 40, 232–4. Abstract

Marshall, W.E. (2014). Bacterial ORNs, a new paradigm to prevent infection. In Weston A. Price Foundation, online Article.

Marshall, W. E. (2010). Oligoribonucleotides alert the immune system of animals to the imminence of microbial infection. U.S. Patent No. 7,678,557. Washington, DC: U.S. Patent and Trademark Office. Article

Nakata, K., Sugi, Y., Narabayashi, H., Kobayakawa, T., Nakanishi, Y., Tsuda, M., ... & Takahashi, K. (2017). Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4. Journal of Biological Chemistry, 292(37), 15426-15433. Abstract

Nishiyama, K., Sugiyama, M., & Mukai, T. (2016). Adhesion properties of lactic acid bacteria on intestinal mucin. Microorganisms, 4(3), 34. Abstract

Parker, R. B. (1974). Probiotics, the other half of the antibiotic story. Anim Nutr Health, 29, 4-8.

Parvez, S., Malik, K.A., Kang, S., & Kim, H.Y. (2006). Probiotics and their fermented food products are beneficial for health. J Appl Microbiol. 100, 1171–85. Article

Roberfroid, M.B. (2000). Prebiotics and probiotics: Are they functional foods? Am J Clin Nutr, 71, 1682S–7S. Article

Saini, R., Saini, S., Sugandha. (2009). Probiotics: The health boosters. J Cutan Aesthet Surg, 2, 112. Letter

Salas-Jara, M. J., Ilabaca, A., Vega, M., & García, A. (2016). Biofilm forming Lactobacillus: new challenges for the development of probiotics. Microorganisms, 4(3), 35. doi:10.3390/microorganisms403003

Shmaryahu, A., Carrasco, M., & Valenzuela, P. D. (2014). Prediction of bacterial microRNAs and possible targets in human cell transcriptome. Journal of Microbiology, 52(6), 482-489. Abstract

Staedel, C., & Darfeuille, F. (2013). Micro RNA s and bacterial infection. Cellular microbiology, 15(9), 1496-1507. Abstract

Sunkavalli, U., Aguilar, C., Silva, R. J., Sharan, M., Cruz, A. R., Tawk, C., ... & Eulalio, A. (2017). Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia. PLoS pathogens, 13(4), e1006327. Abstract

Wahid, F., Shehzad, A., Khan, T., & Kim, Y. Y. (2010). MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1803(11), 1231-1243.  https://doi.org/10.1016/j.bbamcr.2010.06.01

Zhao, Y., & Lukiw, W. J. (2018). Microbiome-mediated upregulation of microRNA-146a in sporadic Alzheimer’s disease. Frontiers in neurology, 9, 145. Article

IBS:  Inflammatory Bowel Support

Balakrishnan, M., & Floch, M. H. (2012). Prebiotics, probiotics and digestive health. Current Opinion in Clinical Nutrition & Metabolic Care, 15(6), 580-585. Abstract

Dimidi, E., Christodoulides, S., Scott, S. M., & Whelan, K. (2017). Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Advances in Nutrition, 8(3), 484-494. Article

Distrutti, E., Monaldi, L., Ricci, P., & Fiorucci, S. (2016). Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World journal of gastroenterology, 22(7), 2219. Article

Ghouri, Y. A., Richards, D. M., Rahimi, E. F., Krill, J. T., Jelinek, K. A., & DuPont, A. W. (2014). Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clinical and experimental gastroenterology, 7, 473. Article

Lin, P.W., Myers, L.E., Ray, L., Song, S.C., Nasr, T.R., Berardinelli, A.J., Kundu, K., Murthy, N., Hansen, J.M., & Neish A.S. (2009). Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation. Free Radic. Biol. Med, 47, 1205–1211. doi: 10.1016/j.freeradbiomed.2009.07.033.

Martini, E., Krug, S. M., Siegmund, B., Neurath, M. F., & Becker, C. (2017). Mend your fences: the epithelial barrier and its relationship with mucosal immunity in inflammatory bowel disease. Cellular and Molecular Gastroenterology and Hepatology, 4(1), 33-46. Article

Patel, R., & DuPont, H. L. (2015). New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clinical Infectious Diseases, 60(suppl_2), S108-S121. https://doi.org/10.1093/cid/civ177

Pedersen, G. (2000). Development, validation and implementation of an in vitro model for the study of metabolic and im-mune function in normal and inflamed human co-lonic epithelium. Autoimmunity, 32, 255-263. Article

Vanderpool, C., Yan, F., & Polk, B. D. (2008). Mechanisms of probiotic action: implications for therapeutic applications in inflammatory bowel diseases. Inflammatory bowel diseases, 14(11), 1585-1596. https://doi.org/10.1002/ibd.20525

Vitetta, L., Briskey, D., Alford, H., Hall, S., & Coulson S. (2014). Probiotics, prebiotics and the gastrointestinal tract in health and disease. Inflammopharmacology, DOI: 10.1007/s10787-014-0201-4. Article

Wasilewski, A., Zielińska, M., Storr, M., & Fichna, J. (2015). Beneficial effects of probiotics, prebiotics, synbiotics, and psychobiotics in inflammatory bowel disease. Inflammatory bowel diseases, 21(7), 1674-1682. Abstract

Zhang, Y., Li, L., Guo, C., Mu, D., Feng, B., Zuo, X., & Li, Y. (2016). Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: a meta-analysis. BMC gastroenterology, 16(1), 62. Abstract

Modulating a Healthy Microbiome: Immunity, Intestinal Barrier & Brain

Arora, T., & Bäckhed, F. (2016). The gut microbiota and metabolic disease: current understanding and future perspectives. Journal of internal medicine, 280(4), 339-349. Article

Blackwood, B. P., Yuan, C. Y., Wood, D. R., Nicolas, J. D., Grothaus, J. S., & Hunter, C. J. (2017). Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. Journal of probiotics & health, 5(1). Article

Bosscher, D., Breynaert, A., Pieters, L., & Hermans, N. (2009). Food-based strategies to modulate the composition of the microbiota and their associated health effects. Journal of physiology and pharmacology/Polish Physiological Society.-Kraków, 1991, currens, 60(S: 6), 5-11. Article

Bron, P. A., Kleerebezem, M., Brummer, R. J., Cani, P. D., Mercenier, A., MacDonald, T. T., ... & Wells, J. M. (2017). Can probiotics modulate human disease by impacting intestinal barrier function?. British Journal of Nutrition, 117(1), 93-107. Abstract

Cani PD, Delzenne NM. (2011).The gut microbiome as therapeutic target. Pharmacol Ther, 130(2), 202-12.DOI: 10.1016/j.pharmthera.2011.01.012

Choudhury, T. G., & Kamilya, D. (2018). Paraprobiotics: an aquaculture perspective. Reviews in Aquaculture. Abstract

de Vos, P., Mujagic, Z., de Haan, B. J., Siezen, R. J., Bron, P. A., Meijerink, M., ... & Troost, F. J. (2017). Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells. Frontiers in Immunology, 8, 1000. DOI:

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De Vrese, M., & Schrezenmeir, J. (2008). Probiotics, prebiotics, and synbiotics. Adv. Biochem. Eng. Biotechnol, 111, 1–66. Abstract

Dinan, T. G., & Cryan, J. F. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. The Journal of physiology, 595(2), 489-503. Article

Gibson, G.R., Probert, H.M., van Loo, J.A.E., & Roberfroid, M.B. (2004). Dietary modulation of the human colonic microbiota: Updating the concept of prebiotics. Nutr. Res. Rev, 17, 257–259. Abstract

Gibson, G.R., & Roberfroid, M.B. (1995). Dietary modulation of the colonic microbiota: Introducing the concept of prebiotics. J. Nutr, 125, 1401–1412. Abstract

Hu, S., Wang, L., & Jiang, Z. (2017). Dietary Additive Probiotics Modulation of the Intestinal Microbiota. Protein and peptide letters, 24(5), 382-387. DOI:10.2174/0929866524666170223143615

Kechagia, M., Basoulis, D., Konstantopoulou, S., Dimitriadi, D., Gyftopoulou, K., Skarmoutsou, N., & Fakiri, E. M. (2013). Health benefits of probiotics: a review. ISRN nutrition, 2013.  http://dx.doi.org/10.5402/2013/481651

Macfarlane, S. M. G. T., Macfarlane, G. T., & Cummings, J. T. (2006). Prebiotics in the gastrointestinal tract. Alimentary pharmacology & therapeutics, 24(5), 701-714. Article

Maguire, M., & Maguire, G. (2019). Gut dysbiosis, leaky gut, and intestinal epithelial proliferation in neurological disorders: towards the development of a new therapeutic using amino acids, prebiotics, probiotics, and postbiotics. Reviews in the Neurosciences, 30(2), 179-201. Article

Manzoni, P., Mostert, M., Leonessa, M. L., Priolo, C., Farina, D., Monetti, C., ... & Gomirato, G. (2006). Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clinical infectious diseases, 42(12), 1735-1742. Article

Mujagic, Z., De Vos, P., Boekschoten, M. V., Govers, C., Pieters, H. J. H., De Wit, N. J., ... & Troost, F. J. (2017). The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial. Scientific reports, 7, 40128. DOI:10.1038/srep40128

Nishiyama, K., Sugiyama, M., & Mukai, T. (2016). Adhesion properties of lactic acid bacteria on intestinal mucin. Microorganisms, 4(3), 34. Abstract

Patel, R., & DuPont, H. L. (2015). New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clinical Infectious Diseases, 60(suppl_2), S108-S121. Abstract

Roberfroid M. (2007). Prebiotics: The concept revisited. J. Nutr, 137, 830–837. Article

Roberfroid, M. B. (2002). Functional foods: concepts and application to inulin and oligofructose. British Journal of Nutrition, 87(S2), S139-S143. https://doi.org/10.1079/BJN/2002529

Sirisinha, S. (2016). The potential impact of gut microbiota on your health: Current status and future challenges. Asian Pac J Allergy Immunol, 34(4), 249-264. Article

Thomas, L. V., Suzuki, K., & Zhao, J. (2015). Probiotics: a proactive approach to health. A symposium report. British Journal of Nutrition, 114(S1), S1-S15. Abstract

Tufarelli, V., & Laudadio, V. (2016). An overview on the functional food concept: prospectives and applied researches in probiotics, prebiotics and synbiotics. J Exp Bioland Agric Sci, 4(3), 273-8. Article

Tsilingiri, K., & Rescigno, M. (2012). Postbiotics: what else?. Beneficial microbes, 4(1), 101-107. Abstract

Vitetta L., Sali A. (2008). Probiotics, prebiotics and gastrointestinal health. Med. Today, 9, 65–70. Article

Yin, X., Lee, B., Zaragoza, J., & Marco, M. L. (2017). Dietary perturbations alter the ecological significance of ingested Lactobacillus plantarum in the digestive tract. Scientific reports, 7(1), 7267. Abstract

Babies and Young Children’s Microbiome

Amenyogbe, N., Kollmann, T. R., & Ben-Othman, R. (2017). Early-life host–microbiome interphase: the key frontier for immune development. Frontiers in pediatrics, 5, 111. DOI:10.3389/fped.2017.00111

Blanton, L. V., Barratt, M. J., Charbonneau, M. R., Ahmed, T., & Gordon, J. I. (2016). Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science, 352(6293), 1533-1533. DOI: 10.1126/science.aad9359

Cox, M. J., Huang, Y. J., Fujimura, K. E., Liu, J. T., McKean, M., Boushey, H. A., ... & Lynch, S. V. (2010). Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome. PLoS One, 5(1), e8745. Article

Emami, C. N., Petrosyan, M., Giuliani, S., Williams, M., Hunter, C., Prasadarao, N. V., & Ford, H. R. (2009). Role of the host defense system and intestinal microbial flora in the pathogenesis of necrotizing enterocolitis. Surgical infections, 10(5), 407-417. Abstract

Goldenberg, J. Z., Lytvyn, L., Steurich, J., Parkin, P., Mahant, S., & Johnston, B. C. (2015). Probiotics for the prevention of pediatric antibiotic‐associated diarrhea. The Cochrane Library. Abstract

Hodzic, Z., Bolock, A. M., & Good, M. (2017). The role of mucosal immunity in the pathogenesis of necrotizing enterocolitis. Frontiers in pediatrics, 5, 40.Article

Hayes, S. R., & Vargas, A. J. (2016). Probiotics for the Prevention of Pediatric Antibiotic-Associated Diarrhea. Explore: The Journal of Science and Healing, 12(6), 463-466. https://doi.org/10.1016/j.explore.2016.08.015

Kang, D. W., Ilhan, Z. E., Isern, N. G., Hoyt, D. W., Howsmon, D. P., Shaffer, M., ... & Krajmalnik-Brown, R. (2018). Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe, 49, 121-131. Article

Patel, R.M., & Denning, P.W. (2013). Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: What is the current evidence? Clin Perinatol, 40(1), 11-25. Article

Shankar, V., Gouda, M., Moncivaiz, J., Gordon, A., Reo, N. V., Hussein, L., & Paliy, O. (2017). Differences in gut metabolites and microbial composition and functions between Egyptian and US children are consistent with their diets. Msystems, 2(1), e00169-16. Article

Subramanian, S., Huq, S., Yatsunenko, T., Haque, R., Mahfuz, M., Alam, M. A., ... & Barratt, M. J. (2014). Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature, 510(7505), 417. Abstract

Wegh, C. A., Schoterman, M. H., Vaughan, E. E., Belzer, C., & Benninga, M. A. (2017). The effect of fiber and prebiotics on children’s gastrointestinal disorders and microbiome. Expert review of gastroenterology & hepatology, 11(11), 1031-1045. https://doi.org/10.1080/17474124.2017.1359539

Zhang, M., Ma, W., Zhang, J., He, Y., & Wang, J. (2018). Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China. Scientific reports, 8(1), 13981. Article

Metabolic Support: Cardiovascular, Diabetes, Cancer, and Weight

Cani, P.D., Pssemiers, S., Van de Wiele, T., Guiot, Y., Everad, A., Rottier, O…. Delzenne, N.M. (2009). Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2 driven improvement of gut permeability. Gut, 58(8), 1091-1103. DOI:10.1136/gut.2008.165886

Cani, P. D. (2019). Severe obesity and gut microbiota: does bariatric surgery really reset the system?. Gut, 68(1), 5-6. Abstract

Cani, P. D., & Delzenne, N. M. (2009). The role of the gut microbiota in energy metabolism and metabolic disease. Current pharmaceutical design, 15(13), 1546-1558. Article

Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes, 57(6), 1470-1481. Article

Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., ... & Waget, A. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56(7), 1761-1772. Article

Cani, P. D., Neyrinck, A. M., Fava, F., Knauf, C., Burcelin, R. G., Tuohy, K. M., ... & Delzenne, N. M. (2007). Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia, 50(11), 2374-2383. Article

Druat, C., Alligier, M., Salazar, N., Neyrinck, A.M., & Delzenne, N.M. (2014). Modulation of the gut microbiota by nutrients with prebiotic and probiotic properties. Adv Nur, 5(5), 624S-633S. DOI:10.3945/an.114.005835

Everard, A., & Cani, P. (2013). Diabetes, obesity and gut microbiota. Best Pract. Res. Clin. Gastroenterol, 27, 73–83. Article

Falcinelli, S., Rodiles, A., Hatef, A., Picchietti, S., Cossignani, L., Merrifield, D. L., ... & Carnevali, O. (2017). Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish. Scientific reports, 7(1), 5512. Article

Frazier, T. H., DiBaise, J. K., & McClain, C. J. (2011). Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. Journal of Parenteral and Enteral Nutrition, 35(5_suppl), 14S-20S. Article

Han, J. L., & Lin, H. L. (2014). Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. World journal of gastroenterology: WJG, 20(47), 17737. Article

Korkmaz, O. A., Sadi, G., Kocabas, A., Yildirim, O. G., Sumlu, E., Koca, H. B., ... & Bilgehan, M. Lactobacillus helveticus and Lactobacillus plantarum modulate renal antioxidant status in a rat model of fructose-induced metabolic syndrome. Article

Macfarlane, S., Cleary, S., Bahrami, B., Reynolds, N., & Macfarlane, G. T. (2013). Synbiotic consumption changes the metabolism and composition of the gut microbiota in older people and modifies inflammatory processes: a randomised, double‐blind, placebo‐controlled crossover study. Alimentary pharmacology & therapeutics, 38(7), 804-816. Article

Marques, F. Z., Mackay, C. R., & Kaye, D. M. (2018). Beyond gut feelings: how the gut microbiota regulates blood pressure. Nature Reviews Cardiology, 15(1), 20. Article

Qin, Y., Roberts, J. D., Grimm, S. A., Lih, F. B., Deterding, L. J., Li, R., ... & Wade, P. A. (2018). An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Genome biology, 19(1), 7. Article

Roberfroid, M., Gibson, G. R., Hoyles, L., McCartney, A. L., Rastall, R., Rowland, I., ... & Guarner, F. (2010). Prebiotic effects: metabolic and health benefits. British Journal of Nutrition, 104(S2), S1-S63. Abstract

Serino, M., Blasco-Baque, V., Nicolas, S., & Burcelin, R. (2014). Managing the manager: gut microbes, stem cells and metabolism. Diabetes & metabolism, 40(3), 186-190. Abstract

Yan Q, Li X, Feng B. (2015). The efficacy and safety of probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: study protocol for a randomized, double-blinded, placebo controlled trial of the Probiotics Prevention Diabetes Programme (PPDP). BMC Endocr Discord; 15(1): 74. Article

Cardiovascular and Fatty Liver Support

Álvarez-Mercado, A. I., Navarro-Oliveros, M., Robles-Sánchez, C., Plaza-Díaz, J., Sáez-Lara, M. J., Muñoz-Quezada, S., ... & Abadía-Molina, F. (2019). Microbial Population Changes and Their Relationship with Human Health and Disease. Microorganisms, 7(3), 68. Article

Delzenne, N. M., Knudsen, C., Beaumont, M., Rodriguez, J., Neyrinck, A. M., & Bindels, L. B. (2019). Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut–liver axis. Proceedings of the Nutrition Society, 1-10. Abstract

Fernandes, R., do Rosario, V. A., Mocellin, M. C., Kuntz, M. G., & Trindade, E. B. (2017). Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: A systematic review. Clinical Nutrition, 36(5), 1197-1206. Abstract

Iacono, A., Raso, G. M., Canani, R. B., Calignano, A., & Meli, R. (2011). Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms. The Journal of nutritional biochemistry, 22(8), 699-711. Article

Johnson-Henry et al. (2008). Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli 0157:H7- Induced changes in epithelial barrier function. Infect Immun; 76:1340-1348. Abstract

Lee et al. (2006). Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta; 1761: 736-744. Article

Safari, Z., & Gérard, P. (2019). The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cellular and Molecular Life Sciences, 1-18. Abstract

Shalitin, S., Battelino, T., & Moreno, L. A. (2019). Obesity, Metabolic Syndrome and Nutrition. Nutrition and Growth: Yearbook 2019, 119, 13-42.  Chapter

Wang et al. (2009). Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet. Appl Microbiol Biotechnol; 84: 341-347. Abstract

Yadav et al. (2007). Antidiabetic effect of probiotic dahl containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition; 23: 62-68. Article

Yari, Z., & Hekmatdoost, A. (2019). Dietary Interventions in Fatty Liver. In Dietary Interventions in Gastrointestinal Diseases (pp. 245-255). Academic Press. Abstract

The Microbiome & Support During Cancer

Alexander, J. L., Kohoutova, D., & Powell, N. (2019). Science in Focus: The Microbiome and Cancer Therapy. Clinical Oncology, 31(1), 1-4. Abstract

Arora, M., Baldi, A., Kapila, N., Bhandari, S., & Jeet, K. (2019). Impact of Probiotics and Prebiotics on Colon Cancer: Mechanistic Insights and Future Approaches. Current Cancer Therapy Reviews, 15(1), 27-36. Article

Banerjee, S., & Robertson, E. S. (2019). Future Perspectives: Microbiome, Cancer and Therapeutic Promise. In Microbiome and Cancer (pp. 363-389). Humana Press, Cham. Abstract

Belcheva, A., Irrazabal, T., & Martin, A. (2015). Gut microbial metabolism and colon cancer: can manipulations of the microbiota be useful in the management of gastrointestinal health?. Bioessays, 37(4), 403-412. Abstract

Buford, T. W. (2017). (Dis) Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome, 5(1), 80. Article

Chen, B., Du, G., Guo, J., & Zhang, Y. (2019). Bugs, drugs, and cancer: can the microbiome be a potential therapeutic target for cancer management?. Drug discovery today. Article

De Almeida, C. V., de Camargo, M. R., Russo, E., & Amedei, A. (2019). Role of diet and gut microbiota on colorectal cancer immunomodulation. World journal of gastroenterology, 25(2), 151.  Article

Dewar, M., Izawa, J., Li, F., Chanyi, R. M., Reid, G., & Burton, J. P. (2018). Microbiome.In Bladder Cancer (pp. 615-628). Academic Press. Chapter32

Drago, L. (2019). Probiotics and Colon Cancer. Microorganisms, 7(3), 66. Article

Femia, A. P., Luceri, C., Dolara, P., Giannini, A., Biggeri, A., Salvadori, M., ... & Caderni, G. (2002). Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats. Carcinogenesis, 23(11), 1953-1960. Article

Han, C. Dai, Y.Q., Hua, Z-C., Fu, G.F., Yin, Y., Hu, B., & Xu, G.X. (2019). Bifidobacterium as a delivery system of functional genes for cancer therapy. In A.M. Chakrabarty & A.M. Fialho (Eds.), Microbial infections and cancer therapy (pp. 1-32). Singapore: Pan Stanford Publishing Pte. Ltd. Chapter1

Helmink, B. A., Khan, M. W., Hermann, A., Gopalakrishnan, V., & Wargo, J. A. (2019). The microbiome, cancer, and cancer therapy. Nature medicine, 1. Article

Hibberd, A. A., Lyra, A., Ouwehand, A. C., Rolny, P., Lindegren, H., Cedgård, L., & Wettergren, Y. (2017). Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ open gastroenterology, 4(1), e000145. Abstract

Li, W., Deng, Y., Chu, Q., & Zhang, P. (2019). Gut microbiome and cancer immunotherapy. Cancer letters. Article

Liong, M. T. (2008). Roles of probiotics and prebiotics in colon cancer prevention: postulated mechanisms and in-vivo evidence. International journal of molecular sciences, 9(5), 854-863. Abstract

Mazraeh, R., Azizi-Soleiman, F., Jazayeri, S. M. H. M., & Noori, S. M. A. (2019). Effect of inulin-type fructans in patients undergoing cancer treatments: A systematic review. Pakistan Journal of Medical Sciences, 35(2). Abstract

Nicoletti, A., Pompili, M., Gasbarrini, A., & Ponziani, F. R. (2019). Going with the gut: probiotics as a novel therapy for hepatocellular carcinoma. Hepatobiliary Surgery and Nutrition. Editorial

Raza, M. H., Gul, K., Arshad, A., Riaz, N., Waheed, U., Rauf, A., ... & Arshad, M. (2019). Microbiota in cancer development and treatment. Journal of cancer research and clinical oncology, 145(1), 49-63. Abstract

Sharma, A. (2019). Importance of Probiotics in Cancer Prevention and Treatment. In Recent Developments in Applied Microbiology and Biochemistry (pp. 33-45). Academic Press. Abstract

Sethi, V., Vitiello,

BioImmersion Probiotic Master Blend – Probiotics- Bifidobacterium longum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus and streptococcus thermophilus; Prebiotic- Inulin from chicory Root; Supernatant- probiotic metabolites, and ORNs. 15 billion CFU.

Capsule- Cellulose & Water

SUPERNATANT— The supernatant is designed to address hospital generated infections.*

Hospital generated infections: Take 2-4 during a hospital stay, or if infected with organisms such as C. difficile (causing diarrhea). It is used to address salmonella, food poisoning, yeast overgrowth, etc. It is also supportive with colitis, diverticulitis, and Crohn’s disease.*

Colds and flu: Take 1-2 capsules a day. Add 1 teaspoon of Lact ORNs and dissolve in mouth. Add 1-2 capsules of Garlic.*

ASD (autistic spectrum disorder): many health care providers find the Supernatant is well tolerated by children with ASD. If 1 capsule is too much, open up the capsule and mix half the amount of the powder with water.*

An everyday probiotic: Due to its strong protection and ability colonize and compete against pathogens, the Supernatant is an excellent choice for everyday probiotic. Take 1-2 daily as maintenance.*

Our Favorite: The Supernatant is such an advanced probiotic product. Our CEO, Seann Bardell, considers it his most favorite product, alongside the Garlic, Phyto Power,and Fructo Borate.

As a probiotic mix it helps even the most sensitive people!*