How To Use Prebiotics For Enhanced Microbiome And Human Health
This article will outline how to build the probiotic flora by supporting levels of pre-biotics and by adding certain pre-biotic foods into the diet. Many times when the GI Map or other microbiome tests are performed there is an “insufficiency dysbiosis” – where lack of the probiotics species is an important issue to correct. The gut immunity is maintained by probiotics, and these require proper prebiotic foods to be maintained.
Short Chain Fatty Acids, Key to Health Benefits
SCFA’s are formed upon dietary carbohydrates, oligosaccharides and soluble fiber fermentation by some gut bacteria. The most common SCFA is lactate followed by acetic, propionic, butyrate and minor levels of isobutyrate, others are also produced.
SCFA’s are secreted especially by bacteria from the phyla Bacteroidetes and Firmicutes that can be found at high concentrations in the large intestine. Butyrate and proprionate production in the colon is represented in the figure below, Note the Firmucutes and Bacteroidetes phyla vary in amounts in the proximal to the distal colon, with the Firmicutes getting the first chance to ferment incoming prebiotic foods:
In general the Firmicultes phylum facilitate butyrate production (it includes Faecalibacterium prausnitzii and the probiotic Clostridium spp. with substrates of carbohydrates as well as fats, prebiotic oligosaccharides such as inulin and galactans as well as soluble fiber assisting butyrate production.
Bacteroidetes family tend to produce proprionic acid and these require a more whole-grain foods eg oats, lentils and others with soluble fiber, but some use any remaining protein.
Most of us think of the critical probiotics as being the Lactobacillus or Bifidobacterium species. However, these are not the cornerstone probiotics species: Akkermansia muciniphila and Faecalibacterium prausnitzii perform even more fundamental protection of the gut, liver and, metabolism and immune system as we will see below.
SCFAs and the probiotics species:
- Lactobacillus species are the primary producers of lactate. Lactate produced by Lactobacillus provides an unfavourable environment for many gram-negative bacteria by disrupting the outer membrane, thus reducing viability of Escherichia coli O157:H7, Pseudomonas aeruginosa, and Salmonella enterica. PMID: 10788373
- Bifdobacterium produce acetate over butyrate, they facilitate colonization of Faecalibacterium prausnitzii. Faecalibacterium prausnitzii is the primary probiotic producing butyrate.
- Butyrate is the key energy source for local colonocytes and stimulates healthy tight junctions between these cells.
- Faecalibacterium prausnitzii produces butyrate to regulate NF-kB, macrophage activity and maintain Th17/Treg balance to ameliorate colorectal colitis
- F. prausnitzii causes anti-inflammatory effects by inhibiting interleukin (IL)-6/signal transducer histone deacetylase doi.org/10.1093/ibd/izy182
- Clostridium species such as Cluster IV and XIV also produce butyrate.
- Probiotic Clostridium butyricum is the most important single species of the Clostridium clusters.
- Clostridium butyricum increased the expression of lipogenesis- or lipolysis-related proteins, reducing rancidity of liver fats. PMID: 23696823
- Clostridium butyricum and its produced butyrate also substantially decreased the expression of the tight-junction proteins intestinal zonula occluden-1 and occludin. PMID: 23696823
- Clostridium butyricum treated rats also showed remarkable induction of Nrf2 and its associated antioxidative enzymes, which suppressed hepatic oxidative stress. Sodium butyrate given alone had the same effect. PMID: 23696823
- Butyrate imprints potent antimicrobial activity during macrophage differentiation
- The probiotic metabolite, n-butyrate, exerts immunomodulatory effects on intestinal macrophages and renders them hyporesponsive to commensals that reside in the colon, reducing unnecessary inflammatory responses. DOI: 10.1073/pnas.1322269111
Other probiotics that raise butyrate are Clostridium butyricum, L. rhamnosus, L. plantarum, L. paracasei and Enterococcus raffinosus, Enterococcus avium and Enterococcus faecalum. FOS, oat fiber and resistant starch form potatoes also feed the Butyrate production naturally.
A short side note on the keto and FODMAP diets – they reduce butyrate species:
With its avoidance of grains there is a loss of soluble fiber and carbohydrates, which are a source of energy for creating short chain fatty acids. In fact, besides a decrease of Bifidobacteria, a 47% reduction of total bacterial load and of F. prausnitzii and Clostridium Cluster IV levels were also observed, along with marked reduction of Akkermansia muciniphelia
Halmos EP, Christophersen CT, Bird AR, et al
Diets that differ in their FODMAP content alter the colonic luminal microenvironment Gut 2015;64:93-100
What do the SCFA’s like butyrate do?
SCFA’s have a positive affect gut motility, and intestinal mucus secretion, inhibit colon cancer by initiation of apoptosis, stimulate insulin-like growth factor, reduce inflammation and assist lower systemic blood pressure. These multitudinous effects promote the SCFAs and the foods and microbiota that promote them to great prominence for health. DOI 10.3389/978-88945-941-4
Butyrate is the local energy source for colonocytes and also it plays an important role in maintenance of the gut barrier function through stimulation of tight junction integrity and mucin production.
SCFAs, especially butyrate, appear to exert regulatory effects on gluconeogenesis and lipogenesis mediated by PPARγ (PMID: 25695945) and protein kinases, protecting against a high-fat diet–induced obesity via a PPARg-dependent switch from lipogenesis to fat oxidation. (DOI: 10.2337/db14-1213). Therefore SCFA’s produced by probiotics are involved in the regulation of fat and glucose metabolism in a wide range of cell types, especially benefitting the liver.
Do we know this benefit occurs in human studies?
The metabolic health of nearly 1,000 people in the Netherlands was found to correlate with the presence of certain bacteria and bacterial metabolic pathways. Most notably, higher faecal levels of butyrate predicted better insulin responses. The study also showed that participants’ genes partially predict the level of butyrate production in people’s guts, and microbiome structure more broadly — a finding confirmed in a different group of more than 4,000 individuals.
Then came the test of causality. If altered insulin sensitivity changes the microbiome (rather than the microbiome disrupting insulin physiology), all genetic factors known to influence insulin sensitivity should also predict a person’s butyrate production. But they did not. https://doi.org/10.1038/s41588-019-0350-x
This suggests that the microbiome structure is affected by diet, and when altered through butyrate and through inflammation produced by the endotoxin from gram negative dysbiotic species, where LPS then raise systemic NF-kB, IL-6 and TNF-a, which affects the insulin responses that in turn disrupt insulin signaling as well as fat metabolism.
Types of Prebiotic Fiber Supplements – Feeding the Key Probiotics:
Soluble fiber includes beta glucans, pectins, inulin, guar gum and psyllium. It is fermentable by GI bacteria in the ileum and colon, generating SCFA’s which are anti-inflammatory and feed the gut endothelial and gut associated organs especially the liver. Psyllium husk is 70% soluble fiber.
Prebiotics for butyrate production
Potato starch, a resistant starch is associated with elevated butyrate levels in the large bowel of humans, rats and pigs. Oligosaccharides, galactans, oats and other soluble fiber such as psyllium and resistant starch from rice also feed the butyrate production naturally. During an oat bran intervention (60 g oat bran (corresponding to 20 g dietary fiber) fecal butyrate concentration increased by 36% at 4 weeks.
Inulin
Inulin is a fructan, one of the FODMAPS. We have already shown FODMAPs are needed to benefit Akkermansia and the appropriate Clostridial clusters producing butyrate in a chart above.
Inulin is found in leeks, onions, garlic, asparagus, chicory root, and burdock root. Inulin is best known for its ability to sustain increases in populations of Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii and Eubacterium. Eubacterium are another important butyrate-producing species indigenous to the bowel. By escaping digestion and absorption in the small intestine, inulin arrives largely intact in the colon where it increases the proportion of the butyrate producer Faecalibacterium prausnitzii also Bifidobacterium, assisting colon health
Inulin is ideal for establishing the more desirable probiotics, and assists butyrate production.
Inulin is found in nearly all the Klaire Labs probiotic products, such as Klaire Therbiotic Powder and in their prebiotic supplement BiotaGen.
Arabinogalactan
This prebiotic fiber is a polysaccharide derived from the heartwood of Western Larch tree. It is an excellent source of dietary fiber, and has been approved as such by the FDA. It has been shown to increase the production of short-chain fatty acids, principally butyrate and propionate, It increases Bifidobacteria and Lactobacillus, as well as Akkermansia muciniphila. Larch arabinogalactan’s has a mild taste and good solubility in water that make it a relatively easy to employ in paediatric populations.
Arabinogalactans feature is that it enhances immune function:
- Promoting immune cytokine production, including the IL-12 from dendritic cells that stimulate the innate systems macrophages, and the adaptive Thymic Th-1 immune cell functions, cytotoxic NK Cells and increase antiviral IFN-g
- Increasing the number and activity of natural killer cells. A number of chronic diseases are characterised by decreased NK cell activity, including chronic fatigue syndrome, viral hepatitis, CMV, EBV & autoimmune diseases such as multiple sclerosis.
- Significantly decreased the incidence of cold episodes (by 23%) by enhancing the barrier defenses to viruses and activating dendritic cell function to Th1 and IFN-g activation. PMID: 23339578
- Reduces Morganella and the p cresol that it produces. P cresol damages the intestinal and the epidermal layers causing leaky gut and leaky skin.
- Promotes Akkermansia mucinophilia, with excellent anti-inflammatory and metabolic syndrome management benefits
INL can provide arabinogalactans in three products:
- Klaire Biotagen, also containing inulin and beta glucan.
- It is in a pure form in the Vital Nutrients Arabinogalactan product.
- Arabiogalactan is something of a specialist prebiotic, given when seeking to provide immune support. If that is required the Medlab Immune 5 is our recommended way to introduce arabinogalactan along with well-selected probiotic Lactobacillus species, lactoferrin and colostrum in the product.
Beta-glucan.
One of the ingredients in many mushrooms as well as in Saccharomyces bourlardii and in oats. It is a glucose polysaccharide fermentable prebiotic found in soluble fiber.
Beta glucan has been shown to
- Lower cholesterol. Research studies have demonstrated that increasing soluble fiber intake by 5-10 g/day can reduce LDL cholesterol by some 5%.
- For greater LDL cholesterol reductions, the National Heart, Lung, and Blood Institute’s Therapeutic Lifestyle Changes (TLC) diet recommends soluble fiber intakes up to 25 g/day. The World Health Organization (WHO) suggests worldwide consumption of soluble fiber of greater than 25 g/day as well, considerably above the average consumption.
- Experimentally beta glucan is shown to increase lysozyme concentrations – which is anti Streptococcal. DOI: 10.1126/science.628841
Klaire labs BiotaGen® is one product recommended for Beta Glucan support, also with inulin, and arabinogalactan. When increasing fiber intake, go slowly and drink plenty of water to reduce GI side effects. Oats breakfasts or psyllium can be recommended. Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower after 24–26 weeks in a psyllium supplemented group (given 5g twice daily) than in the placebo group (P < 0.001). doi.org/10.1093/ajcn/72.4.1066. Similar results are seen with oats fiber.
Resistant starch
Sourced from maize or cooked then cooled rice or potatoes. This is a carbohydrate that resist digestion in the small intestine and ferments in the large intestine. As the fibers ferment they act as a prebiotic and feed the probiotics in the gut. In particular acetate, butyrate and propionate are produced.
A randomized, double-blinded and crossover design clinical trial was conducted using resistant starch (RS). The study subjects were given either 40 g high amylose RS2 or energy-matched control starch with three identical diets per day throughout the study. The effect of RS was evaluated by monitoring body fat, glucose metabolism, gut hormones, gut microbiota, short-chain fatty acids (SCFAs) and metabolites. The visceral and subcutaneous fat areas were significantly reduced following RS intake. Acetate and early-phase insulin, C-peptide and glucagon-like peptide-1 (GLP-1) secretion were increased, and the low-density lipoprotein cholesterol (LDL-C) and blood urea nitrogen (BUN) levels were decreased after the RS intervention. [doi.org/10.1038/s41598-018-38216-9].
The metabolic benefits were partly mediated by Akkermansia muciniphila, which were increased by the resistant starch.
What Is Akkermansia muciniphila?
It turns out to be the most crucial of app probiots for the health of the epithelial layer, and especially the mucin layer. It is highly anti-inflammatory and tends to block endotoxin entry to the circulation. There is also cross-talk between Akkermansia muciniphila and intestinal epithelium that controls diet-induced obesity. One study demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that controled inflammation, assisted the gut barrier, and supported gut peptide secretion. https://doi.org/10.1073/pnas.1219451110.
The intestinal abundance of Akkermansia was the main predictor of total free fatty acid (FFA) serum levels, where high Akkermansia levels caused reduced serum FFA and IL-6 (the pro-inflammatory cytokine) levels in a study of 101 Spanish people. PMID: 28791008
To briefly introduce the benefits of Akkermansia the figure below represents an obese phenotype on the left, with dysbiosis and high LPS, whereas with increased Akkermansia, as on the right, LPS and its metabolic effects are blocked. In animal experiments this has an anti-obesity effect.
Resistant starch and arabinogalactan prebiotics both increase Akkermansia.
- Plantains and green bananas (as a banana ripens the starch changes to a regular starch)
- Beans, peas, and lentils (white beans and lentils are the highest in resistant starch)
- Whole grains including oats and barley
- Cooked and cooled rice or potatoes. The amount of resistant starch changes with heat. Oats, green bananas, and plantains lose some of their resistant starch when cooked. Cooked rice and potatoes that have been cooled is higher in resistant starch than rice that was cooked and not cooled.
