Pomegranate for Akkermansia and butyrate producing species
There is some clinical human trial research showing efficacy for weight loss, and supported by animal research. Eat more Pomegranate! and a little of the inner pith too!
This post is about the wonders of eating more pomegranate products for our gut microbiome, our weight, our blood lipids, and probably for a better mood too!
'Tis the season... to eat pomegranate fresh in the Northern hemisphere, and to freeze or dry some of the peel to have throughout the year. The fresh seeds can simply be frozen to have as a crunchy but slightly mushier fruit snack later in the year too.
Presence of Akkermansia muciniphila in a study subject’s gut microbiome was associated with conversion of ellagic acid into the postbiotic urolithin A, when given from pomegranate or as an isolate. Only 70% of people had conversion to the postbiotic and presence of Akkermansia muciniphila seemed to be the difference. (Henning, et al., 2017) That is the gut species associated with the microbiome of people who ‘happen’ to live to be one hundred years old or more. What is their secret? Good zinc intake and resistant starches?
A double-blind parallel, randomized, placebo-controlled clinical trial (n=68), on the benefits of Pomegranate Juice or Pomegranate Juice plus Inulin (resistant starch) for promoting weight loss in overweight or obese subjects, found more of a shift towards butyrate production and postbiotic pomegranate metabolites (urolithin A and B) in the group who received both Inulin and Pomegranate Juice. Two hundred milliliters of pomegranate juice was provided which is ~ 6.5 ounces. (Hou, et al., 2024) Paywall, I don’t see how much inulin was provided from the Abstract alone.
“Moreover, PJ+inulin treatment also promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites, which correlated with the abundance of the bacterial genus. Our results suggested that PJ supplemented with inulin modulates gut microbiota composition and thus promotes the production of microbiota-associated metabolites that exert potential beneficial effects in overweight/obese subjects.” (Hou, et al., 2024)
A review article from 2023 summarizes the species shift which pomegranate intake seems to promote - more beneficial butyrate species and a reduction in harmful species:
“Intake of pomegranate promotes beneficial bacteria in GM (e.g. Lactobacillus spp., Bifidobacterium spp.) while reducing the growth of harmful bacteria (e.g. Bacteroides fragilis group, Clostridia). Akkermansia muciniphila, and Gordonibacter spp., among others, biotransform PU and EA into Uro. Uro contributes to strengthening intestinal barrier and reducing inflammatory processes. Yet, Uro production varies greatly among individuals and depend on GM composition. Uro-producing bacteria and precise metabolic pathways need to be further elucidated therefore contributing to personalized and precision nutrition.” (Yin, et al., 2023)
Is Akkermansia muciniphila a negative species? It doesn’t seem to be, summary Brave AI with a definite link to living past 100 years old, but maybe balance is key. Some of the species may help the intestinal mucus layer while too much may be too much.
Full Abstract, clinical trial, n = 20, (Li, et al., 2015):
“The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.” (Li, et al., 2015)
People who were overweight, with or without Metabolic Syndrome, were examined for urolithin metabolites after eating either walnuts, other nuts, or pomegranate, and it blood markers for inflammation and cardiovascular health were measured. It was observed that the people who were producing urolithin A had healthy blood labs than the people who were found to be producing urolithin B or isourolithin-A. (Selma, et al., 2018) The plot thickens - life is complex.
“[Urolithin Metabolite] UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d).” (Selma, et al., 2018)
Pomegranate fruit pulp (PFP) was given in a study on diet-induced obesity in mice and it helped physical biomarkers of body weight, blood glucose and lipids and changed the balance of gut species in a way that correlated with the improved biomarkers. Lack of the Akkermansia muciniphila was associated with worse weight and blood labs and the pomegranate fruit pulp enriched the balance of that species and others. (Song, et al., 2022)
“Our results showed that PFP treatment reduced HFD-induced body weight gain by 35.23% (P < 0.05), steatosis scores by 50% (P < 0.05) and insulin resistance by 56.84% (P < 0.05), compared with the mice fed HFD alone. Moreover, compared with the mice in the HFD group, PFP supplement changed the composition of the gut microbiota, and enriched Akkermansia muciniphila, Parabacteroides distasonis, Bacteroides acidifaciens, Mucispirillum schaedleri and Lachnospiraceae bacterium 28-4, which were negatively correlated with physical biomarkers, including body weight, glucose, triglycerides and total cholesterol.” (Song, et al., 2022)
The difference between Urolithin A and Urolithin B producers was looked at with a computer simulated model called TWIN-SHIME. (García-Villalba, et al., 2017) *Fulltext available, all the rest of these links have a paywall.
“Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.” (García-Villalba, et al., 2017)
A review of research by Verhoog, et al., 2019 provides a list of substances including pomegranate that have shown benefit for promoting Akkermansia muciniphila and Faecalibacterium prausnitzii, both of which are abundant in the fecal samples of healthy individuals.
Presence of A. muciniphila was reduced by a lack of “fermentable oligosaccharides, disaccharides, monosaccharides, and polyols” but was helped by a calorie restricted diet, and their presence was increased in studies that provided supplementation with either:
pomegranate extract,
resveratrol,
polydextrose,
yeast fermentate,
sodium butyrate and/or
inulin.
By promoting butyrate producing species, pomegranate products can also be increasing butyrate and other short chain fatty acids.
Studies on F. prausnitzii mainly studied supplementation with “prebiotics (e.g. fructo-oligosaccharides, inulin type fructans, raffinose)” and mixed results were observed with a tendency toward promoting growth of the species rather than inhibiting it or having no effect. (Verhoog, et al., 2019)
“Overall, 29 unique trials were included, of which five examined A. muciniphila, 19 examined F. prausnitzii, and six examined both, in a total of 1444 participants. A caloric restriction diet and supplementation with pomegranate extract, resveratrol, polydextrose, yeast fermentate, sodium butyrate, and inulin increased the abundance of A. muciniphila, while a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols decreased the abundance of A. muciniphila. For F. prausnitzii, the main studied intervention was prebiotics (e.g. fructo-oligosaccharides, inulin type fructans, raffinose); seven studies reported an increase after prebiotic intervention, while two studies reported a decrease, and four studies reported no difference.” (Verhoog, et al., 2019)
Pudding power!
Netflix show quote: “Why do you eat pudding? (Like a little kid?)”
The answer: “Pudding makes me happy.” It literally could be increasing our happiness by improving our gut microbiome and shifting what it makes more towards happy serotonin and dopamine.
*The show is called Lie to Me and is a great education in seeing and understanding the microexpressions of body language. What is a Poker Tell? That varies from person to person, but we all have some shared tendencies. (imdb.com)
An animal-based study by Salsinha, et al., 2024, looked at countering negative effects of the standard Western diet (~ high fat-high sugar was the experimental diet compared to a Control diet) with use of omega-3 containing fish oil and punic acid containing pomegranate oil. The team found beneficial effects for the animal’s gut microbiome balance. (Salsinha, et al., 2024) The improved tyrosine levels suggest that the combination of taking fish oil and pomegranate oil could help improve a person’s mood.
“The effect of Fish oil (omega-3 source) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota modulation were determined by subjecting the oil samples to in vitro fecal fermentations. Cecal samples from rats from two different dietary groups: a control diet (CD) and a high-fat high-sugar diet (WD), were used as fecal inoculum. 16S amplicon metagenomics sequencing showed that Fish oil + Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Moreover, tyrosine concentrations, a precursor for dopamine and norepinephrine, increase in the Fish oil + Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a potential positive impact of these oils' mixture on gut-brain axis modulation.” (Salsinha, et al., 2024)
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.
Reference List
(García-Villalba, et al., 2017) García-Villalba R, Vissenaekens H, Pitart J, Romo-Vaquero M, Espín JC, Grootaert C, Selma MV, Raes K, Smagghe G, Possemiers S, Van Camp J, Tomas-Barberan FA. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract. J Agric Food Chem. 2017 Jul 12;65(27):5480-5493. doi: 10.1021/acs.jafc.7b02049. Epub 2017 Jun 28. PMID: 28616977. https://pubs.acs.org/doi/10.1021/acs.jafc.7b02049 *Fulltext
(Henning, et al., 2017) Henning SM, Summanen PH, Lee RP, Yang J, Finegold SM, Heber D, Li Z. Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo. Anaerobe. 2017 Feb;43:56-60. doi: 10.1016/j.anaerobe.2016.12.003. Epub 2016 Dec 7. PMID: 27940244. https://pubmed.ncbi.nlm.nih.gov/27940244/
(Hou, et al., 2024) Hou C, Shi H, Xiao J, Song X, Luo Z, Ma X, Shi L, Wei H, Li J. Pomegranate Juice Supplemented with Inulin Modulates Gut Microbiota and Promotes the Production of Microbiota-Associated Metabolites in Overweight/Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial. J Agric Food Chem. 2024 Jul 3;72(26):14663-14677. doi: 10.1021/acs.jafc.4c00849. Epub 2024 Jun 18. PMID: 38887904. https://pubmed.ncbi.nlm.nih.gov/38887904/
(Li, et al., 2015) Li Z, Henning SM, Lee RP, Lu QY, Summanen PH, Thames G, Corbett K, Downes J, Tseng CH, Finegold SM, Heber D. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers. Food Funct. 2015 Aug;6(8):2487-95. doi: 10.1039/c5fo00669d. Epub 2015 Jul 20. PMID: 26189645. https://pubmed.ncbi.nlm.nih.gov/26189645/
(Salsinha, et al., 2024) Salsinha AS, Cima A, Araújo-Rodrigues H, Viana S, Reis F, Coscueta ER, Rodríguez-Alcalá LM, Relvas JB, Pintado M. The use of an in vitro fecal fermentation model to uncover the beneficial role of omega-3 and punicic acid in gut microbiota alterations induced by a Western diet. Food Funct. 2024 Jun 4;15(11):6095-6117. doi: 10.1039/d4fo00727a. PMID: 38757812. https://pubmed.ncbi.nlm.nih.gov/38757812/
(Selma, et al., 2018) Selma MV, González-Sarrías A, Salas-Salvadó J, Andrés-Lacueva C, Alasalvar C, Örem A, Tomás-Barberán FA, Espín JC. The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome. Clin Nutr. 2018 Jun;37(3):897-905. doi: 10.1016/j.clnu.2017.03.012. Epub 2017 Mar 16. PMID: 28347564. https://pubmed.ncbi.nlm.nih.gov/28347564/
(Song, et al., 2022) Song H, Shen X, Chu Q, Zheng X. Pomegranate fruit pulp polyphenols reduce diet-induced obesity with modulation of gut microbiota in mice. J Sci Food Agric. 2022 Mar 30;102(5):1968-1977. doi: 10.1002/jsfa.11535. Epub 2021 Sep 24. PMID: 34514612. https://pubmed.ncbi.nlm.nih.gov/34514612/
(Verhoog, et al., 2019) Verhoog S, Taneri PE, Roa Díaz ZM, Marques-Vidal P, Troup JP, Bally L, Franco OH, Glisic M, Muka T. Dietary Factors and Modulation of Bacteria Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: A Systematic Review. Nutrients. 2019 Jul 11;11(7):1565. doi: 10.3390/nu11071565. PMID: 31336737; PMCID: PMC6683038. https://pmc.ncbi.nlm.nih.gov/articles/PMC6683038/ *Fulltext
(Yin, et al., 2023) Yin Y, Martínez R, Zhang W, Estévez M. Crosstalk between dietary pomegranate and gut microbiota: evidence of health benefits. Crit Rev Food Sci Nutr. 2024;64(27):10009-10035. doi: 10.1080/10408398.2023.2219763. Epub 2023 Jun 19. PMID: 37335106. https://pubmed.ncbi.nlm.nih.gov/37335106/