As Primer™ is primarily a prebiotic, let’s start with those. Prebiotics have come a long way since oat bran and psyllium husks. Beginning with inulin, a huge array of oligosaccharide and glycan type compounds have been found to be fermented and fed on by intestinal bacteria. These newer prebiotics tend to be basically tasteless and dissolve effortlessly, which is quite handy.
With the importance of microbial diversity for optimal gut and body health, we want a number of different prebiotics for them to feed on. Likewise, we want to choose the ones that best increase the bacteria we want to increase, rather than just randomly feeding all of them.
GOS reduced fat mass, food intake by 14%, and elevated expression of pro-satiety peptides. Combining them with Calcium increased propionate formation (116). In addition to reductions in food intake, appetite, bodyweight, and inflammation are also decreased (117). GOS increase beneficial bacteria, particularly Bifidobacterium, with 5-10 fold increases in some subjects being noted (118-121). They also raise Bacteroides levels (121). They are long-acting, providing prebiotic effect throughout the entire length of the colon, while strongly inhibiting pathogenic bacteria (122). This owes to high resistance to conditions early in gut digestion (123).
GOS provide direct enhancement of intestinal barrier function through interaction with goblet cells, separate from SCFA or anti-inflammatory mediated mechanisms. They also showed a 2-4 fold mucin elevation, which would create a positive environment for mucin feeders such as Akkermansia and Bacteroides (124). They inhibited inflammatory responses, augmented protein junction assembly by 85%, and prevented loss of barrier function (125). GOS displayed a microbiota independent increase in tight junction assembly and improved barrier function (126). Finally, they mitigate LPS induced inflammation and protect against stress induced LPS activity (127, 128).
AXOS are strongly Bifidogenic. They increase satiety inducing peptides, while decreasing weight gain, fat mass, and insulin resistance (129). They raise butyrate levels along with Bifidobacterium suggestive of subsequent cross-feeding to butyrate producing bacteria (130). They also reduce protein fermentation in the gut (130, 131). This spares amino acids for more useful purposes as well as preventing toxic breakdown products.
AXOS are long-acting, with bacterial fermentation occurring throughout length of colon. They significantly promote Bacteroides as well as Lactobacillus (132). They are even better than inulin at providing fermentation products to the distal portions of the colon (133). AXOS elevated Roseburia and butyrate levels, with total SCFA increases as high as 2-3 fold (134, 135). Finally, they increase tight junction proteins, improve barrier function, and inhibit inflammation in adipose tissue (129).
XOS increased Bifidobacterium along with acetate and butyrate. Combining with inulin further augmented butyrate formation, as well as increasing propionate, suggesting cross-feeding to butyrate and propionate producing bacteria like Roseburia and Bacteroides (136, 137). And, XOS have indeed been found to promote both Roseburia and Bacteroides, as well as improving the Firmicutes:Bacteroides ratio (138, 139). Bacteroides possess special xylan degrading enzymes, making them a preferred fermenter of XOS (140). Elevated Bacteroides and butyrate from XOS protected against genotoxicity in a colonic simulator (141). They also decreased LPS and increased epithelial cell proliferation (137, 142).
Lactulose inhibits adipogenesis and fat accumulation, down-regulates adipogenic genes, and reduces caloric extraction efficiency, while increasing energy expenditure and lipolysis (143). It also improves post-prandial blood glucose and insulin levels (144, 145). Lactulose raises Bifidobacterium counts, particularly of the ideal cross-feeder B. adolescentis, as well as Akkermansia (146-148). Finally, it decreases intestinal permeability and proteolysis of amino acids in the gut (147, 149).
Inulin improved glucose uptake in insulin resistant cells, and activated AMPK (150). It increases Bifidobacterium and butyrate, while reducing protein fermentation (151, 152). It has a prolonged Bifidogenic effect, with more distal fermentation and SCFA production vs. fructo-oligosaccharides, particularly of butyrate and propionate – again, suggestive of cross-feeding (153, 154). In fact, it was found to increase B. adolescentis more than 4-fold and F. Prausnitzii by 50% (155). It also increased Roseburia, while augmenting mucin production 6-fold, leading to large elevations in Akkermansia and propionate, distally (156).
Resistant Starch 3 (RS3)
Resistant Starch 3 is formed when starchy foods such as potatoes and rice are cooked and then cooled. This turns formerly digestible starches into resistant starches via a process called retrogradation. RS3 is particularly, and somewhat uniquely, highly prebiotic for Ruminococcus bromii, with increases up to 4-fold (157-159). R. bromii has superior ability to degrade this resistant starch, which is the most prevalent fermentable carbohydrate in the average diet, making it a “keystone species” by acting as a cross-feeder for other species (160, 161).
It was also found to be readily consumed by Bacteroides, elevating faecal propionate, rather than butyrate as is often observed following resistant starch feeding of other types. This propionate formation reflects a gut community dominated by the Bacteroides, and it actually became the primary lineage in this study (162).
Amylopectin was found to be superior to several other prebiotics for increasing butyrate, as well as butyrate producers F. prausnitzii and Roseburia (163). It also raises Bacteroides, with increases in Roseburia and Bacteroides being found to be proportional to the amylopectin content of barley and oats (164, 165).
Mucin is the glycoprotein constituent of the mucus which lines the wall of the intestines and protects it. Several species of bacteria, including some of the really good ones, feed off of it. Akkermansia is the most well characterized mucin consumer (166, 167). Verrucomicrobia, of which Akkermansia is the primary genus, was increased from .03% to 5.25% by mucin, and in combination with inulin, Bacteroides was raised as well (168).
Bacteroides thetaiotamicron is a known mucin degrading specialist (169-171). Bacteroides fragillis consumes mucins as well (172, 173). Roseburia intestinalis also colonizes the mucosal layer and feeds on mucins (174).
With these bacteria colonizing the mucus and being close to the epithelium, particularly with the butyrate producers, bioavailability for epithelial cell regeneration and barrier function is enhanced.
Rhamnose is a preferred sugar for the propanediol pathway of propionate production by Roseburia inulinivorans (175, 176). It is quite selectively metabolized to propionate (177, 178). It is much more selective for propionate formation than lactulose or glucose, which utilize different, less selective pathways, resulting in 4 times more propionate than with lactulose or glucose (179). Rhamnose was also found to decrease triglyceride synthesis and serum triglyceride levels, likely due to propionates effects on the SCFA receptors FFAR 2/3 (180).
Glutamine is the primary substrate of rapidly diving cells, a category to which the epithelial cells of the digestive tract belong. It increases tight junction protein production (181). It does so by activating the mammalian target of rapamycin (mTOR) cell signaling in enterocytes. It enhances intestinal growth, enterocyte proliferation and survival, and regulates intestinal barrier function in injury, infection, stress, inflammation, and other catabolic conditions (182). It is basically both the leucine (protein) and the glucose (carbohydrate), to go along with butyrate as the fat, for the fueling of survival, growth, and reproduction of the enterocyte. This makes it quite possibly the most important nutrient for intestinal barrier health and function.
Glutamine also reduces utilization of other amino acids (asparagine, aspartate, serine, lysine, leucine, valine, ornithine, and arginine) in the gut, preserving them for more useful things while reducing toxic metabolites (183, 184). It decreases intestinal permeability and enhances intestinal mucosa and barrier function (185). Glutamine improves intestinal barrier impairment and quells the LPS mediated inflammatory cascade (186). It also prevents mucosal injury and promotes recovery from LPS induced inflammatory damage, as well as downregulating TLR-4 expression (187, 188).
Inflammatory conditions increase the requirements for Glutamine to maintain the intestinal barrier (189). It has specifically been shown to protect the intestinal barrier against processed, Western diet style foods (190). AMPK mediates its enhancement of tight junction integrity and barrier preservation (191).
Conversion to glutamate and subsequent cellular uptake is a pivotal step in its protective effects (192). Monosodium Glutamate has been found to promote the colonization of F. prausnitzii and Roseburia (193). And, finally, L-glutamate enhances barrier function (194).
Increasing dietary Calcium produced a reduction in weight gain and fat pad mass of 26-39% with a 51% inhibition of adipocyte fatty acid synthase expression and activity, while stimulating lipolysis by 3 to 5-fold (195). In another study, an almost 50% increase in weight loss was found (196). A high-Calcium diet decreased fat gain by 55%, stimulated adipose tissue uncoupling protein (UCP2) and skeletal muscle UCP3 expression, increased thermogenesis and lipolysis, while lowering fatty acid synthase expression and activity (197, 198). Calcium also elevated peptides GLP-1 and GLP-2, which increase satiety and decrease food intake (199, 200).
Calcium improves intestinal permeability, strengthens the mucosal barrier, reduces inflammation, and alleviates colitis (201). Prebiotics have actually been found to have negative effects on intestinal permeability and inflammation without Calcium Phosphate rather than the positive effects produced when it is present (202, 203). This protection is dependent on Phosphate, thus Calcium likely pulls it into the colon, improving luminal buffering capability (204). This is because SCFAs produced by prebiotic fermentation could lower pH too much in its absence.
Finally, Calcium is necessary for the Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CaMKK2) mediated AMPK signaling and barrier maintenance produced by Glutamine (205).
Multi-berry powder has the power of berries!! A day’s worth of Primer™ is equal to ¼ cup of mixed berries. It has the polyphenols and fiber and such that berries have, but it is mostly in here because it gives it a nice, subtle berry flavor.
Primer™ takes the concept of prebiotic far beyond where anyone has previously taken it before. It starts by carefully and selectively feeding the most beneficial bacterial species, including novel probiotic species that you cannot attain, anywhere. It does so in a way that no other product comes even close to doing. It protects against dysfunction of the gut and microbiota to promote better health, better appetite control, better metabolism, and better fat loss. Finally, its supporting ingredients go to work on making your inflamed and leaky gut as good as new, leaving your body functioning in the optimal way it is intended to.
Primer™ is a gourmet meal for your microbiota and a happy-ending massage for your gut. It is a one of a kind product that fits in perfectly with and enhances any diet and exercise program, any supplement regimine, any lifestyle.
For references, see "View Full Science Write-Up" here: http://neobium.org/product-line/primer/