Abstract Verbatim : Whole plant foods, including fruit, vegetables, and whole grain cereals, protect against chronic human diseases such as heart disease and cancer, with fiber and polyphenols thought to contribute significantly. These bioactive food components interact with the gut microbiota, with gut bacteria modifying polyphenol bioavailability and activity, and with fiber, constituting the main energy source for colonic fermentation. In humans, whole grain cereals can modify fecal bacterial profiles, increasing relative numbers of bifidobacteria and lactobacilli. Polyphenol-rich chocolate and certain fruits have also been shown to increase fecal bifidobacteria. The recent FLAVURS study provides novel information on the impact of high fruit and vegetable diets on the gut microbiota. Increasing whole plant food consumption appears to upregulate beneficial commensal bacteria and may contribute toward the health effects of these foods.
Plant polyphenols are a class of chemically diverse secondary metabolites that possess many different biological activities both within the plant and in the animals which eat these plants. They have long been studied for their interactions with mammalian physiological processes that play a role in chronic human disease. They are antioxidants and possess inherent free radical scavenging abilities. Plant polyphenols have the potential to affect certain risk factors of cardiovascular disease such as plasma lipid oxidation state, endothelial function, and platelet aggregation; protect against cancer by reducing DNA damage, cell proliferation, and metastasis; modulate immune function; inhibit bacterial pathogens; and protect against neurological decline.
Some 1000 species of bacteria are known to make up the microbiota in the human gut. They play an important role in human health and disease, and interindividual variation in microbiota makeup influences the profile of metabolites released from dietary components that reach the colon and may also affect an individual’s risk of chronic disease.
There are a limited number of “enterotypes” within the human gut microbiota characterized by a predominance of Prevotella, Bacteroides, and/or Ruminococcus.
Dietary changes in carbohydrates and fats can alter the makeup of one’s microbiota within 24 hours. 6 Different profiles of gut bacteria have also been characterized in populations with chronic immune or metabolic-related diseases including inflammatory bowel disease (IBD), celiac disease, diabetes, and obesity.
Typically, these conditions present with lower prevalence of beneficial butyrate-producing bacteria, such as Faecalibacterium prausnitzii, and the bifidobacteria, which appear to be indicative of a well-functioning, healthy saccharolytic type microbiota. In dysbiotic microbiomes, there is a high prevalence of Enterobacteriaceae, a phylum that includes many important gastrointestinal pathogens including Escherichia coli, Shigella, Salmonella, Campylobacter, and Helicobacter. These diseases too are often associated with increased intestinal permeability or “leaky gut”.
There has been found to be differences in the gut microbiomes of obese and lean individuals:
The obese appear to be typified by a gut microbiota with a reduced Bacteroidetes/Firmicutes ratio and perturbations within important fiber-degrading saccharolytic populations
Rural African children, following a traditional diet rich in whole plant foods, had a microbiota composition strikingly different from that of their European counterparts. Their microbiota was dominated by Bacteroidetes, notably the Prevotella and novel fiber-degrading species such as Xylanibacter, whereas the Italian children had a much lower ratio of Bacteroidetes to Firmicutes. The Italian children also had higher relative abundance of enterobacteria, including E. coli, Shigella, and Salmonella. <<<—Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa This plant based diet also resulted in a three fold increase in the relative amount of SCFA (short chained fatty acids) in the stool of Afican children. The bottom line is that poor dietary eating patterns, such as less vegetables and fruit intake results in a dysbiotic microbiome and poorer health as found in obesity, inflammatory bowel diseases, and even certain cancers. > The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population —Abstract is as follows: An obese-type human microbiota with an increased Firmicutes:Bacteroidetes ratio has been described that may link the gut microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat and carbohydrate are modifiable risk factors that may impact on MetS by altering the human microbiome composition. We determined the effect of the amount and type of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid (SCFA) concentrations in people ‘at risk’ of MetS. : A total of 88 subjects at increased MetS risk were fed a high saturated fat diet (HS) for 4 weeks (baseline), then randomised onto one of the five experimental diets for 24 weeks: HS; high monounsaturated fat (MUFA)/high glycemic index (GI) (HM/HGI); high MUFA/low GI (HM/LGI); high carbohydrate (CHO)/high GI (HC/HGI); and high CHO/low GI (HC/LGI). Dietary intakes, MetS biomarkers, faecal bacteriology and SCFA concentrations were monitored. RESULTS: High MUFA diets did not affect individual bacterial population numbers but reduced total bacteria and plasma total and LDL-cholesterol. The low fat, HC diets increased faecal Bifidobacterium (P ¼ 0.005, for HC/HGI; P ¼ 0.052, for HC/LGI) and reduced fasting glucose and cholesterol compared to baseline. HC/HGI also increased faecal Bacteroides (P ¼ 0.038), whereas HC/LGI and HS increased Faecalibacterium prausnitzii (P ¼ 0.022 for HC/HGI and P ¼ 0.018, for HS). Importantly, changes in faecal Bacteroides numbers correlated inversely with body weight (r ¼ 0.64). A total bacteria reduction was observed for high fat diets HM/HGI and HM/LGI (P ¼ 0.023 and P ¼ 0.005, respectively) and HS increased faecal SCFA concentrations (Po0.01). CONCLUSION: This study provides new evidence from a large-scale dietary intervention study that HC diets, irrespective of GI, can modulate human faecal saccharolytic bacteria, including bacteroides and bifidobacteria. Conversely, high fat diets reduced bacterial numbers, and in the HS diet, increased excretion of SCFA, which may suggest a compensatory mechanism to eliminate excess dietary energy.
Obese-type gut microbiota, characterised by a higher Firmicutes:Bacteroidetes ratio in obese as opposed to lean, have been observed both in murine models of obesity and humans. Moreover, germ-free mice colonised with the microbiota from obese mice display increased body fat, higher faecal total energy content (by bomb calorimetry) and higher concentrations of faecal short chain fatty acids (SCFA) compared with their conventionally fed lean counterparts, indicating that the microbiota of obese animals may have an increased capacity to harvest energy.15 In addition, weight loss in humans induced by CHOor fat-restricted diets has been associated with a change in gut microbial composition, resembling the microbiota of lean individuals (that is, increased Bacteroidetes). Data from human studies show higher faecal SCFA concentrations in overweight and obese humans compared with their lean counterparts on a similar Western-style diet. Dietary supplementation studies with the prebiotics inulin or oligofructose in humans and animals have shown that changes in colonic SCFA are accompanied by reduced plasma lipids, particularly in those with hyperlipidaemia and hypercholesterolaemia.
For example in :Balca´zar-Mun˜oz BR, Mart´ınez-Abundis E, Gonza´lez-Ortiz M. Effect of oral inulin administration on lipid profile and insulin sensitivity in subjects with obesity and dyslipidemia. Rev Med Chil 2003; 131: 597 — 604: Abstract as follows:
BACKGROUND: Inulin is a non absorbable polysaccharide with prebiotic effects, whose influence on blood lipidsor insulin sensitivity is not well known: AIM: To assess the effect of oral administration of inulin on lipid profile and insulin sensitivity in dyslipidemic obese subjects. MATERIAL AND METHODS: A clinical trial, double blind, randomized with placebo was carried out in 12 obese, hypertrygliceridemic and hypercholesterolemic subjects between 19 and 32 years old. The subjects were randomized to receive 7 g/day of inulin or placebo in the morning, during 4 weeks. Biochemical and metabolic profiles and euglycemic-hyperinsulinemic clamp technique for assessing insulin sensitivity, before and after pharmacological intervention were performed.
RESULTS: After inulin administration, there was a significant reduction of total cholesterol (248.7 +/- 30.5 and 194.3 +/- 39.8 mg/dL; p = 0.028), low density lipoprotein (LDL), cholesterol (136.0 +/- 27.8 and 113.0 +/- 36.2 mg/dL; p = 0.028), very low density lipoproteins (VLDL) (45.9 +/- 18.5 and 31.6 +/- 7.2 mg/dL; p = 0.046) and trygliceride concentrations (235.5 +/- 85.9 and 171.1 +/- 37.9 mg/dL; p = 0.046). No effect of inulin on insulinsensitivity was observed.
CONCLUSIONS: The oral inulin administration reduced total cholesterol, LDL cholesterol, VLDL and trygliceride levels in dyslipidemic and obese subjects, without modifications in the insulin sensitivity.
The most recent definition of a prebiotic defines a dietary prebiotic as “… a selectively fermented ingredient that results in specific changes, in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health”. There is also strong animal data linking prebiotics with protection from metabolic syndrome, obesity, type 2 diabetes, colon cancer, and IBD and fortifying the gut microbiota against invading gastrointestinal pathogens. < Prebiotic effects metabolic and health benefits.
Plant complex polysacharides are fiber and we consume 20 g/day on average wheras our ancestors consumed 70-120 g/day. Starch is resistant to degradation and reaches the colon unaltered. Food processin g and preparation can affect the amount of dietary starch becoming resistant as well, and likewise, polyphenol-ruch beverages blunt the post-prandial rise of glucose by altering starch digestion. Once these food compounds reach the colon, they become available to the fermentative activities of the human colonic microbiota. Gut microbiota is specifically evolved for the digestion of complex plant polysaccharides, possessing a range of polysaccharide- and glycan-degrading enzymes not present in the human genome <<- Metagenomic analysis of the human distal gut microbiome Thus the gut microbiota has coevolved with us to extract energy from foods we could not otherwise digest ourselves.
The dominant fermentative activity is carbohydrate fermentation leading to the production of the short-chain fatty acids acetate, propionate, and butyrate. They play a role in supplying energy to the heart, brain,muscle and intestinal mucosa and also play mportant roles in human cell differentiation, proliferation, and programmed cell death; regulation of immune function; thermogenesis; and lipid metabolism.
Asdietary fiber and carbohydrates are used up along the colon, the bacteria can switch to using other sources of energy such as proteins and amino acids. The end products of amino acid fermentation include SCFA but also branched-chain fatty acids, amines, indoles, sulfides, and phenols, some of which are potentially harmful, being variably genotoxic, cytotoxic, and carcinogenic.
The more dietary fiber and plant-sources of foods, the higher the SCFA content in the colon. With higher intake of fiber, the bacteria are extended further along the colon before they have to switch to protein/amino acid fermentation. A 3-fold increase in dietary fiber results in a proportional increase in SCFA production by the gut microbiota and extends saccharolytic fermentation into the transverse and distal colon.
Hydrolysis by the gut microbiota can increase the bioavailability of polyphenols and the microbiota also breaks down many complex polyphenols into smaller phenolic acids, which can be absorbed and function in humans. Functions ascribed include to phenolic acid catabolites include antibacterial activities especially against Gram negative species, like the Enterobacteriaea, anti-inflammatory activities, anti-AGE formation, stimulation of xenobiotic degrading enzymes and detoxification processes, and phytoestrogenic activities.
Microbial metabolites of quercetin and chlorogenic acid/caffeic acid, 3,4-dihydroxyphenylacetic acid (ES), and 3-(3,4- dihydroxyphenyl)propionic acid (PS), respectively, could significantly up-regulate GSTT2 expression and decrease COX-2 expression, a modulation seen as protective against colon cancer << — Miene, C.; Weise, A.; Glei, M. Impact of polyphenol metabolites produced by colonic microbiota on expression of COX-2 and GSTT2 in human colon cells (LT97). Nutr. Cancer 2011, 63, 653−662
Ellagic acid (EA) and its colonic metabolites, urolithin-A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one, Uro-A) and urolithin-B (3-hydroxy-6H-dibenzo[b,d]pyran-6-one, Uro-B), modulate the expression and activity of CYP1A1 and UGT1A10 and inhibit several sulfotransferases in colon cancer cell lines (Caco-2). These phase I and phase II detoxifying enzymes are important components of how our bodies deal with toxic and xenobiotic compounds, and increased expression is associated with a reduced risk of colon cancer in laboratory animals << Gonzalez-Sarr ́ ıas, A.; Azorín-Ortun ́ ̃ o, M.; Yań ̃ ez-Gascon, M. J.; ́ Tomas-Barbera ́ n, F. A.; Garc ́ ıa-Conesa, M. T.; Esp ́ ın, J. C. Dissimilar ́ in vitro and in vivo effects of ellagic acid and its microbiota-derived metabolites, urolithins, on the cytochrome P450 1A1. J. Agric. Food Chem. 2009, 57, 5623−5632
Urolithins, from pomegranate, had, however, already been shown to reduce the growth of cancer cells in an animal model of prostate cancer << Seeram, N. P.; Aronson, W. J.; Zhang, Y.; Henning, S. M.; Moro, A.; Lee, R. P.; Sartippour, M.; Harris, D. M.; Rettig, M.; Suchard, M. A.; Pantuck, A. J.; Belldegrun, A.; Heber, D. Pomegranate ellagitanninderived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J. Agric. Food Chem. 2007, 55, 7732−7737
Microbial catabolites might, at least in part, account for the observed anti-inflammatory activity of certain herbal medicines and functional foods: ferulaldehyde, a microbial catabolite of curcumin, has anti-inflammatory properties in vivo in an animal model of LSP-induced septic shock : Ferulaldehyde, a Water-Soluble Degradation Product of Polyphenols, Inhibits the Lipopolysaccharide-Induced Inflammatory Response in Mice
The 3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 3- hydroxyphenylpropionic acid, and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), derived from colonic catabolism of proanthocyanidins, have been shown to reduce the inflammatory response of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), an inflammatory cell wall component from Gram-negative bacteria such as the Enterobacteriaceae. Secretion of IL-6, IL-1, and TNF-α was reduced, suggesting that microbial metabolites may be involved in dampening the inflammatory response to bacterial antigens. <<– Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells
Chlorogenic acid-microbially derived catabolites, dihydrocaffeic acid, dihydroferulic acid, and feruloylglycine, were most effective at protecting cultured neural cells in vitro, indicating that colonic catabolites of dietary polyphenols may play an important role in the improved cognitive function and protection from neuronal degeneration observed in animals fed polyphenol-rich foods such as certain berries.
Urolithins and pyrogallol, microbial ellagitannin-derived catabolites, are highly antiglycative compared to parent polyphenolic compounds in an in vitro model of protein glycation.<<– Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites
Individuals on a Western style, low-fiber diet, the proximal colon is the major site of saccharolytic fermentation, with potentially damaging proteolytic fermentation increasing distally as carbohydrate substrate becomes limiting. Retardation of carbohydrate fermentation in the proximal colon may extend SCFA production to the distal colon, thereby reducing the harmful effects of amino acid catabolites <<–apple proanthocyanidins inhibited both metabolic degradation of short proanthocyanidins and SCFA production : Factors affecting the conversion of apple polyphenols to phenolic acids and fruit matrix to short-chain fatty acids by human faecal microbiota in vitro
Polyphenols have been shown to directly affect the relative abundance of different bacteria within the gut microbiota with tea polyphenols and their derivatives reducing numbers of potential pathogens including Clostridium perfringens and C. difficile and certain Gram-negative Bacteroides spp., with less inhibition toward beneficial clostridia, bifidobacteria, and lactobacilli.
Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured.
Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2) = -0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments.
This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods.
Whole grain breakfast cereals have been shown to mediate a prebiotic modulation of the gut microbiota, giving significant increases in fecal bifidobacteria and/or lactobacilli without changing the relative abundance of other dominant members of the gut microbiota. Also, Ingestion of either whole grain wheat or wheat bran breakfast cereal increased plasma and urine concentrations of ferulic acid, a polyphenol commonly complexed with dietary fiber in whole grain cereals. << Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota a double-blind, placebo-controlled, crossover study
In the FLAVURS group study, they investigated the relative impact of increased fruit and vegetable intake of differing flavonoid content on markers of cardiovascular disease risk. BAsic scheme was: A habitual diet, a high-flavonoid fruit and vegetable diet, or a low-flavonoid fruit and vegetable diet for 18 weeks were compared for health effects. —> Independent analysis of fecal bacteria revealed that in the first cohort (n = 59), dietary intervention with either flavonoid-rich or flavonoid-poor fruits and vegetables significantly increased groups of commensal bacteria important for human health including Bifidobacterium, Atopobium, Ruminococcus, Roseburia, Eubacterium, and Faecalibacterium prausnitzii, whereas the flavonoid-poor diet also increased lactobacilli compared to the control diet.
Chong, M. F.; Geroge, T. W.; Alimbetov, D.; Jin, Y.; Weech, M.; Spencer, J. P. E.; Kennedy, O. B.; Minihane, A.-M.; Gordon, M. H.; Lovegrove, J. A. (For the FLAVURS group) Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increate risk of cardiovascular disease: the FLAVURS Trial. Eur. J. Nutr. 2012, DOI: 10.1007/s00394-012-0343-3.: Abstract below:
Limited robust randomised controlled trials investigating fruit and vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist. We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F&V consumption on nutrient biomarker profile.
A parallel, randomised, controlled, dose–response dietary intervention study. Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week periods during the 18-week study.
Compliance to target numbers and types of F&V was broadly met and verified by dietary records, and plasma and urinary biomarkers. Mean (±SEM) number of F&V portions/day consumed by the HF and LF groups at baseline (3.8 ± 0.3 and 3.4 ± 0.3), 6 weeks (6.3 ± 0.4 and 5.8 ± 0.3), 12 weeks (7.0 ± 0.3 and 6.8 ± 0.3) and 18 weeks (7.6 ± 0.4 and 8.1 ± 0.4), respectively, was similar at baseline yet higher than the CT group (3.9 ± 0.3, 4.3 ± 0.3, 4.6 ± 0.4, 4.5 ± 0.3) (P = 0.015). There was a dose-dependent increase in dietary and urinary flavonoids in the HF group, with no change in other groups (P = 0.0001). Significantly higher dietary intakes of folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P = 0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups compared with CT, which were broadly supported by nutrient biomarker analysis.
The success of improving nutrient profile by active encouragement of F&V intake in an intervention study implies the need for a more hands-on public health approach.
Basis of above is as follows: Up-regulating the Human Intestinal Microbiome Using Whole Plant food and polyphenols and fibers