Mannose, arabinose, xylose, pomegranate peel, oral microbiome and biofilm. **Groundbreaking theoretically.

...and for obesity too

This was an additional topic at the end of a post that was already long, and it took a surprising turn into oral health and how pomegranate may be helping our gut and oral microbiome balance — mannose, xylose, and arabinose can be part of the carbohydrate content of the peel. It is more likely to be present in greater amounts than glucose and fructose when the pomegranate are grown in hotter climates. (Bar-Ya’akov, et al., 2019)

That might explain mixed results in some types of studies - some pomegranate might not have much of mannose, xylose or arabinose and those monosaccharides have medicinal and microbiome benefits. But it also gives us information about other supplements that might help if pomegranate isn't available. It also gives us a clue about synergy - why is whole pomegranate better? Why does it seem like isolated phytonutrients from pomegranate can’t do everything singly that they can perform in the whole fruit extract?

Maybe because of the pectin and monosaccharide starches? Pomegranate peel provides us macronutrients, not just micro nutrients?

• This post is a continuation of the biofilm topic started here: Biofilm, polyphenols, microRNA, MMPs, metastasis, and cancer, (Substack); and continued in Pomegranate Paper relaunch, Mannose, and Herbs for Vitality, (Substack).

To combine the mannose info into this post: Mannose is found in cranberries and other produce in small amounts. Mannose does seem to be helpful against cancer because it is providing nutrients to the person but it starves the cancer cells which need glucose and anaerobic glycolysis for energy. (Luo, et al., 2022) Link via Nattering Naybob.

We likely get a little mannose from a variety of foods. Cranberries are best known for mannose as it has been linked to prevention of UTI bladder infections.

“Mannose can be found in fruits (peaches, apples, oranges, blueberries, black currants, cranberries), legumes (green beans, kidney beans, lima beans, soybeans), vegetables (cabbage, turnip, tomatoes), ivory nuts, Aloe vera and baker’s yeast ^{[2,3,10,11,12]}. The amount of mannose that can be absorbed from these foods in not known ^[3,4].” (nutrientsreview.com)

Aloe vera has wound healing benefits when used topically and the mannose content may aid in that function. (Davis, et al., 1994)

Ketone diets try to starve the cancer from carbohydrates too, but too high fat of a diet would be shifting methylation cycles to the anaerobic pathways too. A moderate carbohydrate diet with 50% or less of calories from fat and no more than 10% of those from saturated fat should help keep methylation cycles chugging along aerobically as long as the many nutrients and cofactors were available.

How much mannose to eat?

I still didn’t find a number but one of the animal studies was providing the mannose supplement as sweetened mannose water. A diet plan that was attempting to be higher than standard in mannose content would need to have less total carbohydrate foods and some refined mannose supplement because no single food is that high in mannose. Some of the pomegranate peel samples had up to 18.1% but no one is going to want to eat just pomegranate peel.

Glucomannan is a fibrous starch from the konjac root and it is a combination of glucose and mannose ~ 50 % mannose. It is quite viscous when hydrated - a thick gooey liquid. It is used as a thickening agent as a food additive or to increase fiber content in a food. It is considered a beneficial oligosaccharide. (Tripetch, et al., 2023) You would want to count it as carbohydrate calories within a diet plan - i.e. swap it for carbohydrate grams being used for bread, starchy veg, milk, fruit, or beans. Too large of a intake could overfeed the gut microbiome and lead to uncomfortable gassiness. Also drink plenty of water when increasing fiber rich foods in the diet.

Only one gram of glucomannan taken three times a day is the recommendation for weight loss purposes.

Mannose may be helping weight in part due to shifts in microbiome species towards less inflammatory species or a more beneficial ratio of Firmicutes to Bacteroidetes species. More on that topic will be discussed later.

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*Liver health… farther along in the post, is where this post started initially at the end of a different post, and I worked through the mannose information to the realization that pomegranate peel helps oral and gut microbiome due to the peel’s arabinose, xylose and mannose content. The special monosaccharide sugars help promote beneficial bacteria which can eat the special sugars and signaling aspects of the chemicals can help break up the biofilm of negative species (Zhang, et al., 2023) which allows our white blood cells to remove them more easily. The way arabinose helps decrease biofilm is by gene regulation - less biofilm will be produced due to signaling by the monosaccharide causing less biofilm to be produced (Zhang, et al., 2023) - that is handy. Thanks Mother Nature.

That also explains why medical research has consistently shown synergistic benefits from use of whole fruit extracts compared to isolated polyphenols or other single isolates or the postbiotic urolithin-A which does have potent benefits. But none of the potent isolates seemed to have all the benefits that whole pomegranate extract showed.

Monosaccharides are macronutrients - a functional food used for energy purposes, not just cofactor or vitamin like roles. That is how I have described the inner pith of pomegranate peel, as a food to eat in tiny teaspoon amounts, rather than being a trace nutrient to have in microscopic capsule amounts. Too much fiber can overfeed our microbiome and then we can regret our hastily eating too much raw fruit or veg or pasta salad. Pectin is also a beneficial fiber found in pomegranate peel.

Plants make more antioxidant and signaling chemicals in harsher climates.

More beneficial phytonutrients are produced in plants that are experiencing harsher growing conditions. That is part of the reason that ‘organic’ produce has more nutrients than found in commercially grown, artificial fertilizer crops.

A microbiome coincidence?

In exploring the topic of mannose I learned that it effects microbiome species (Zhang, et al., 2021) in the same way that pomegranate does, (Singh, et al, 2022), improves the ratio between Firmicutes and Bacteroidetes species. Having too much of the Firmicutes is associated with obesity. Both are beneficial short chain fatty acid producing species though. This seemed coincidental.

Applying the Gibbs rule #39, “There are no coincidences",” led me to the fact that pomegranate peel can contain mannose and also xylose and arabinose and those monosaccharides have similar microbiome effects. They promote a beneficial balance between species and more of the short chain fatty acid producing species. Short chain fatty acids then feed our colon cells and the butyrate can also activate the immune supporting GP109 receptor.

Citrus and pomegranate inner pith are good sources of pectin and other fiber. Photo by Luke Michael on Unsplash

Biofilm may be used as a protective cloak around cavity causing species.

Biofilm enters the story in that the acid producing cavity promoting bacterial species are also biofilm producing - they make a thicker slime goo coating which is difficult for our white blood cells to penetrate. Somehow the special monosaccharides help modify that biofilm in a way that allows proper immune defense. Arabinose helps against dental pathogens. (An, et al., 2022) Oral cavity causing bacteria may help each other - one species forms more of a protective biofilm layer (S. mutans) and another makes extra lactic acid (Veillonella sp.) which both species like and promotes their growth - but which causes cavities in our teeth. (Luo, et al., 2024)

Cavity causing oral bacteria are team players: “The cariogenic bacteria within the oral microbiota do not exist as isolated entities but rather interact and influence each other. To a certain extent, S. mutans creates a lactic acid-rich environment in carious lesions that facilitates the proliferation of Veillonella species¹², which have been shown to promote the growth of S. mutans in biofilm studies²⁴.” (Luo, et al., 2024)

The yeast Candida (oral thrush) also is acid producing & cavity promoting. - Pomegranate is antimicrobial against it too.

Lactic acid producing Candida yeast in the mouth also can be cavity promoting, (Luo, et al., 2024) , and pomegranate is particularly effective against Candida infections in addition to helping against cariogenic bacterial species. Ellagic acid, an anti-fungal phenol, inhibits an aspartic protease enzyme secreted by Candida albicans. (Polya, 2003, viewable at Corilagin)

Pomegranate products are antimicrobial against dental pathogens.

• Oral mouthwash made with pomegranate extract was tested and found effective against: Pseudomonas aeruginosa and Candida albicans, but not against Enterococcus faecalis. (Oliveira Leite, et al, 2014) *I made myself some pom peel extract and froze it in ice cube trays to use a little at a time as a mouthwash alternative and it really feels effective. See this post for the How-To recipe with photos, Essential oils are FAST… (Substack)

• Pomegranate peel extract was compared to chlorhexidine in an oral mouth rinse clinical trial and the PPE reduced all pathogens that were analyzed but was not as effective against S. mutans as the chlorhexidine. (Jacob, B., et al., 2021)

• Use of 30 ml unsweetened pomegranate juice reduced dental plaque in a small clinical trial. Participants were asked to not brush their teeth for 24 hours prior to the study when a sample was taken before and after the juice. (Kote, Kote, Nagesh, 2011)

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Liver health - reduce anger, and reduce fructose and glucose.

And maybe increase use of mannose rich pomegranate peel…

or cranberries (except those are a histamine trigger food).

If I want a healthier liver and body I may need to cut down on angry thinking and on foods with glucose and fructose. Dried fruit may be healthy in moderation but it is concentrated sugar when eaten in excess and that hits the liver and is turned into fats.

Sugar intake, mainly glucose and fructose, within generic diets has increased dramatically during the past century. Hexose, especially glucose, is the most important energy source in living organisms. However, it has been well documented that consuming too much sugar can raise the incidence of many health problems, including diabetes and obesity. Recently, more studies have demonstrated the harmful effects of sugar. For example, one study reported that glucose-fructose syrup (HFCS) enhances intestinal tumor growth in mice via activation of glycolysis and increased synthesis of fatty acids in tumor cells that support tumor growth (1); Another study found that high fructose intake is associated with increased hepatic fatty acid synthesis and marked insulin resistance (2), and a final study showed that dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate (3). More than that, one clinical study among US adults found that consumption of sugar-sweetened beverages (SSBs) is positively associated with total mortality (4).

In addition, high glucose intake and high fructose intake have also been proven to have pro-inflammatory roles for inflammatory diseases. Zhang et al. revealed that high glucose intake exacerbates autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE) by promoting T helper-17 (Th17) cell differentiation (5). Jones et al. found that fructose reprograms glutamine-dependent oxidative metabolism in mononuclear phagocytes to support LPS-induced inflammation (6). Another study found that high-fructose diet (HFrD) elicited endotoxemia, could activate toll-like receptor (TLR) signaling in liver macrophages, and induce liver inflammation (7). Another two studies also reported that dietary simple sugars alter microbial ecology in the gut and promote colitis and EAE in mice (8, 9).” (Zhang, et al., 2021)

Mannose is a similar monosaccharide that has anti-inflammatory properties instead of inflammatory ones.

“We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.” (Zhang, et al., 2021)

Mannose helps the gut microbiome in similar ways as pomegranate juice - improving the ratio of Bacteriodetes to Firmacutes which may have anti-obesity benefits.

Mannose “May Increase Anti-Inflammatory Gut Microbiome”

“Within the past decade, the gut microbiome has been proven to have critical functions in immune homeostasis and inflammation (35, 36). Sharma et al. showed that mannose treatment by drinking-water supplementation prevented weight gain, lowered adiposity, reduced liver steatosis, and improved glucose tolerance during the induction of obesity in high-fat diet (HFD) mice (20). Interestingly, these beneficial effects of mannose were observed only when initiated early in life, but not when provided later. These changes in HFD mice with different ages, coupled with the fact that continuous mannose supplementation is required, made authors postulate that mannose treatment might change gut microbiome in HFD mice. Indeed, they proved that mannose treatment initiated early in life increased the Bacteroidetes to Firmicutes ratio in the gut microbiota of HFD mice, showing an association between gut microbiota composition and the timing of mannose introduction (20). The decrease of the Bacteroidetes to Firmicutes ratio in the gut microbiota has been shown to cause obesity in both mice and human, and the increase of the ratio is positively associated with weight loss (37–39). These findings show that mannose suppressed obesity by increasing the Bacteroidetes to Firmicutes ratio in the gut microbiota.

Importantly, Bacteroides are the most abundant members of Bacteroidetes in the intestinal tract of mammals, and the immunomodulatory activities of Bacteroides have been identified (40–43). Lower levels of Bacteroides in the gut microbiota have been shown to be associated with Inflammatory Bowel Disease (IBD) (40),…” (Zhang, et al., 2021)

That factoid suggests pomegranate may have mannose content. Xylose content found in some peel samples could help explain why pomegranate is so helpful for dental health and microbiome balance. Beneficial species can eat xylose and bad ones can’t.

“Many studies examined the sugars in the pomegranate fruit, mainly in the juice, revealing glucose, and fructose as the main component of the juice sugars (Figure 1). Sugars found in the fruit peel were in some controversy among studies from different countries. It should be noted that those studies were done for different purposes and therefore followed different procedures of extraction and detection that might explain this disagreement. Some of the studies indicated glucose and fructose as the main sugars while others found that xylose and arabinose are the main sugars (Hasnaoui et al., 2014).” (Bar-Ya’akov, et al., 2019)

Where your pomegranate are grown seems to matter - varieties have differing monosaccharide content in the peels. Tunisian and Iranian species had xylose and arabinose predominating as 60% of the sugar content and had 3.4-18.1% mannose. Species from Israel had glucose and fructose as the major sugars.

“Notably, the major sugars that were detected in the peels differed between the varieties grown in Tunisia, Iran and Israel. In the 12 Tunisian varieties, xylose and arabinose represented more than 60% of the total content, followed by galactose (14%), glucose (∼10%), mannose (∼5%), rhamnose (∼4%), and fucose (∼1.5%) (Hasnaoui et al., 2014). Peels from one Iranian variety showed that the main sugar is glucose (44.9–68.1%), followed by galactose (14.6–19.4%), mannose (3.4–18.1%), arabinose (3.1–18.1%), and rhamnose (3.5–6.0%) (Ahmadi Gavlighi et al., 2018). However, in the 29 worldwide varieties grown in Israel, the major sugars were glucose and fructose.” (Bar-Ya’akov, et al., 2019)

A hotter growing climate leads to lower glucose and fructose ratios:

“The varieties grown in Mediterranean climate showed significantly higher levels of glucose and fructose in the juice than those grown in a hotter habitat (Schwartz et al., 2009)” (Bar-Ya’akov, et al., 2019)

Better quality pomegranate juice is whole fruit pressed in a way that includes peel nutrients in the juice without adding so much that the juice is too bitter to enjoy.

Checking the dental pomegranate juice theory - ‘arabinose and dental cariogenic pathogens pubmed’

» Why is drinking pomegranate juice as effective as brushing your teeth? It is sweet…that doesn’t make sense….unless some of the sugar is xylose, arabinose, and mannose.

Arabinose does have an inhibitory effect on the biofilm created by oral bacteria on titanium discs used for oral implants. (An, et al., 2022) Current dental methods wipe out all of the oral microbiome. Strategies using certain sugars can help adjust the mouth species towards beneficial and away from more cariogenic species that form biofilm and produce excess acid (examples include: S. mutans and Streptococcus sobrinus). Protective species seen during early childhood include Rothia, Neisseria, and Haemophilus, while children with dental caries were more likely to have Prevotella spp., S. mutans, and Human herpesvirus 4 (EB virus). Dental cavities seem to involve the overall microbiome balance rather than being specific to one species. (Luo, et al., 2024)

Incidentally, or causally, Prevotella species may be more prevalent in patients with Alzheimer’s dementia. (Taati Moghadam, et al., 2022)

I seem to have dropped the ball on Tibetan Medicine, Ho’oponopono, and self-compassion. *Referring to the other post, which is not finished yet.

Or maybe I picked up the ball on the interconnectedness of life.

Some sugars cause obesity and over-acidity in us and in bacterial species (glucose and fructose) and other sugars promote health in us and in our bacterial species (mannose, xylose, and arabinose).

Galactose is a sugar that can be used in aerobic methylation cycles and therefore is ‘inflammatory’ in that metabolic waste is created from glucose, however it has not been found to be cavity promoting in the way that glucose and fructose have. Galactose has to be converted into glucose first, so it is slower to affect blood sugar levels or insulin than other carbohydrate foods. (intelligentsugar.info/sugars/galactose/)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(An, et al., 2022) An SJ, Namkung JU, Ha KW, Jun HK, Kim HY, Choi BK. Inhibitory effect of d-arabinose on oral bacteria biofilm formation on titanium discs. Anaerobe. 2022 Jun;75:102533. doi: 10.1016/j.anaerobe.2022.102533. Epub 2022 Feb 7. PMID: 35143955. https://pubmed.ncbi.nlm.nih.gov/35143955/

(Bar-Ya’akov, et al., 2019) Bar-Ya'akov I, Tian L, Amir R, Holland D. Primary Metabolites, Anthocyanins, and Hydrolyzable Tannins in the Pomegranate Fruit. Front Plant Sci. 2019 May 17;10:620. doi: 10.3389/fpls.2019.00620. PMID: 31164897; PMCID: PMC6534183. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2019.00620/full

(Braga-Silva and Santos, 2011) Braga-Silva, Lys & Santos, André. (2011). Aspartic Protease Inhibitors as Potential Anti-Candida albicans Drugs: Impacts on Fungal Biology, Virulence and Pathogenesis. Current Medicinal Chemistry. 18. 2401-19. 10.2174/092986711795843182. https://www.researchgate.net/publication/51123515_Aspartic_Protease_Inhibitors_as_Potential_Anti-Candida_albicans_Drugs_Impacts_on_Fungal_Biology_Virulence_and_Pathogenesis

(Davis, et al., 1994) Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc. 1994 Feb;84(2):77-81. doi: 10.7547/87507315-84-2-77. PMID: 8169808.

(Luo, et al., 2022) Luo H, Wang X, Wang Y, Dan Q, Ge H. Mannose enhances the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis. Discov Oncol. 2022 Jan 3;13(1):1. doi: 10.1007/s12672-021-00447-0. PMID: 35201482; PMCID: PMC8777573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777573/

(Luo, et al., 2024) Luo, SC., Wei, SM., Luo, XT. et al. How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective. npj Biofilms Microbiomes 10, 14 (2024). https://doi.org/10.1038/s41522-024-00488-7 https://www.nature.com/articles/s41522-024-00488-7

(Taati Moghadam, et al., 2022) Taati Moghadam M, Amirmozafari N, Mojtahedi A, Bakhshayesh B, Shariati A, Masjedian Jazi F. Association of perturbation of oral bacterial with incident of Alzheimer's disease: A pilot study. J Clin Lab Anal. 2022; 36:e24483. doi:10.1002/jcla.24483 https://onlinelibrary.wiley.com/doi/full/10.1002/jcla.24483

(Tripetch, et al., 2023) Tripetch P, Lekhavat S, Devahastin S, Chiewchan N, Borompichaichartkul C. Antioxidant Activities of Konjac Glucomannan Hydrolysates of Different Molecular Weights at Different Values of pH. Foods. 2023; 12(18):3406. https://doi.org/10.3390/foods12183406 https://www.mdpi.com/2304-8158/12/18/3406

(Zhang, et al., 2023) Zhang M, Luo X, Li X, Zhang T, Wu F, Li M, Lu R, Zhang Y. L-arabinose affects the growth, biofilm formation, motility, c-di-GMP metabolism, and global gene expression of Vibrio parahaemolyticus. J Bacteriol. 2023 Sep 26;205(9):e0010023. doi: 10.1128/jb.00100-23. Epub 2023 Sep 1. PMID: 37655915; PMCID: PMC10521368. https://pubmed.ncbi.nlm.nih.gov/37655915/

(Zhang, et al., 2021) Zhang W, Cheng H, Gui Y, Zhan Q, Li S, Qiao W, Tong A. Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation. Front Immunol. 2021 Sep 27;12:756920. doi: 10.3389/fimmu.2021.756920. PMID: 34646279; PMCID: PMC8502929. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502929/