Tag Archives: microbiome

Whole plant foods and the Microbiome

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.

Intestinal microbiota in inflammatory bowel disease Friend or foe

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism

Pathophysiological role of host microbiota in the development of obesity.

The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease

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

Obesity and the gut microbiota does up-regulating colonic fermentation protect against obesity and metabolic disease

Microbial ecology Human gut microbes associated with obesity

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 effect of the daily intake of inulin on fasting lipid, insulin and glucose concentrations in middle-aged men and women

 

The intestinal microbiome and health.

A healthy gastrointestinal microbiome is dependent on dietary diversity.

 

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.

Probiotics and Prebiotics Present Status and Future Perspectives on Metabolic Disorders

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.

Role of the Gut Microbiome in Uremia A Potential therapeutic target

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

The microbiome and its potential as a cancer preventive intervention

Gut microbiome and metabolic diseases

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

Modulatory Effects of Gut Microbiota on the Central Nervous System How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Gut Microbiota The Brain Peacekeeper.

Role of Resistant Starch in Improving Gut Health, adiposity and insulin resistance

Resistant starch and protein intake enhances fat oxidation and feelings of fullness in lean and overweight obese women.

Modulation of Gut Microbiota−Brain Axis by Probiotics, Prebiotics, and diet

‘The way to a man’s heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk

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

 

Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota a review

Gut Microbiota, Intestinal Permeability, Obesity-Induced Inflammation, and Liver Injury

Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.

Metabolic endotoxaemia is it more than just a gut feeling

Fermented Rhizoma Atractylodis Macrocephalae alleviates high fat diet-induced obesity in association with regulation of intestinal permeability and microbiota in rats

Probiotics- Interaction with gut microbiome and antiobesity potential

Maturation of Oral Microbiota in Children with or without Dental Caries.

Role of the microbiome in energy regulation and metabolism.

Role of Intestinal Microbiome in Lipid and Glucose Metabolism in Diabetes Mellitus

Getting Personal About Nutrition

More than just a gut instinct-the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome.

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

Diet Effects in Gut Microbiome and Obesity

The art of targeting gut microbiota for tackling human obesity.

Towards microbial fermentation metabolites as markers for health benefits of prebiotics

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.

Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study <<–  Abstract:

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.

RESULTS:

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.

CONCLUSION:

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. 

Effects of cocoa flavanols on risk factors for cardiovascular risk

Diet, gut microbiome, and bone health.

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:

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Fatty acids from diet and microbiota regulate energy metabolism.

 

High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects.

Review article dietary fibre-microbiota interactions.

Obesity Reduces Cognitive and Motor Functions across the Lifespan.

 

 

 

Review of natural products actions on cytokines in inflammatory bowel disease

The strawberry Composition, nutritional quality, and impact on human health

Ellagic acid, pomegranate and prostate cancer — a mini review

 

 

Basis of above is as follows: Up-regulating the Human Intestinal Microbiome Using Whole Plant food and polyphenols and fibers

 

 

 

 

 

 

 

Vaginal Microbiome – Misguided bacteria result in pre-term labor and affects the child’s microbiome.

As a prelude to this article – I just want to explain that this particular article regarding the human microbiome, although obscure at first, ties in later to other areas that affect human health and dieting decisions. I will incorporate that information in time, but I decided to start with this particular aspect due to new information that is coming out and how such a seemingly obscure issue like bacteria in the vagina could possibly have any impact on you. For pregnant women and their newborns, it certainly does since pre-term labor  is costly to society and on a personal level. Also, what is alluded to in the articles below are that a number of modifying issues combine together to create an outcome. For example, poor dental hygiene may have an association with fetal outcomes and general health. Likewise, the mother’s  microbiome is affected by antibiotic use and is passed down to the neonate during delivery. This  external influence impacts the long term health of the child. I’m sorry if this article is not ‘sexy’ but it ties in to a longer running discussion. In an age of increasing use of probiotics and antibiotics, this type of information is evidence-based and not testimonial in nature. It will hopefully lead to a healthier outcome.   – 10/10/2015

I’m going to discuss some research into microbiome-related information that has implications in quite a few areas. Of course, the latest raging research has involved increasing data regarding the trillions of bacteria that are a part of our bodies and the results of alterations in their composition. Over time, I will be writing about various evidence-based research and implications they may have for our health. One area that I see as under-served in the general health maintenance is dental care. I see a great connection with poor dental care and the possibility that it increases the rate of bad outcomes in pregnancy as related to the microbiome composition in individuals with periodontal disease during pregnancy. Of course medicaid and other insurance covers for health maintenance in other ways, but rarely does it cover dental care in the general public. It is expensive to have teeth and maintain them with general care. Between regular checkups, fillings, root canals, and crowns, a single tooth can cost several thousand dollars to spare! Hence, many people have bad teeth and bad bacteria in their mouths, which leads to generalized inflammation throughout the body. JAMA just revealed a piece in the latest issue linked below that discusses premature labor and it’s relationship to the microbiome. One study cited in the article made a clear observation of the association with dental bacteria and premature labor and poor outcomes in neonates: Here is the PDF link below:

Another Frontier in Microbiome Research: Preterm Birth

Another Frontier in Microbiome Research: Preterm Birth

Pre term birth rates

CDC site on pre term labor

The basic research is pointing more and more at general inflammation as a cause of many human illnesses. This inflammation comes from many sources. This is one more example of the association of that inflammation as related to our microbiome and poor outcomes. Let’s discuss the article:

One of the primary research articles cited in the JAMA essay included this one:

Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Prelabor Rupture of Membranes

Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes.

  • The United States has one of the highest rates of pre-term birth, at 12%, it is higher than Canada, Mexico, Europe, and many Latin American Nations.
  • Pre-term birth is a leading cause of death and neurological disability.
  • Bacteria can invade the amniotic cavity to set up infection and inflammation that results in early delivery. In the article above, bacterial DNA from the vagina, gut, and oral area have been found in the amniotic fluid. The MORE DNA found, the earlier the delivery.
  • Higher levels of Lactobacillus in the vaginal area are associated with better outcomes of the fetus and less pre-term delivery.
  • In the study above, samples from the vagina, saliva,stool, and gums were taken in 9 week intervals from 40 women who were pregnant and outcomes were followed. Of the samples, 62% were Lactobacillus-poor and this was inversely correlated with gestational age at delivery. In other words, a UNhealthy oral, gut, and vaginal microbiome was associated with pre-term delivery. In fact 75% of the subjects who had Lactobacillus dominant vaginal microbiota had a term pregnancy that was normal.
  • Microbial Invasion of the amniotic cavity  (MIAC) in pre-mature rupture of the membranes (which results in early delivery) was discovered in half of the test subjects when using MOLECULAR PCR techniques , whereas it was found only in 34 %  by culture. In other words, past research missed bacterial invasion on the amniotic fluid in past studies and underrepresented the importance and types of bacteria that cause and result in pre-term delivery.
  • It appears that Lactobacillus specied protect against poor pregnancy outcomes by producing proteins and lactic acid which modifies the immune response and promotes vaginal health during pregnancy.
  • It was found that by using molecular techniques, the number of invading species of bacteria was some 46 species-level phylotypes, whereas culture historically showed only 14 species. Also, new , uncultivated taxa were discovered to be involved. Included in taxa detected by PCR were some species associated with the gastrointestinal tract (Coprobacillus sp.), the mouth (Rothia denticariosa) and the vagina in the setting of bacterial vaginosis (Atropobium vaginae).
  • If a person’s PCR molecular test was positive for bacteria, the chance of getting a uterine infection during pregnancy (choramnionitis) was at a risk of 2.1, whereas a positive culture showed a risk of 2.0. Also found was that bacterial rDNA abundance was in a dose relationship with gestational age delivery, meaning that more bacterial DNA detected by PCR was associated with pre-mature birth.
  • The strength of the PCR findings was bolstered by the association of higher inflammatory WBC counts in amniotic fluid, as well as IL-6, another marker of inflammation. Patients with positive culture and PCR results (molecular based study) had even higher levels of WBC and IL-6 markers than PCR positive cases alone. The  risk of choramnionitis was trending higher in patients with positive PCR results than in those with just positive culture results. The bottom line is the presence of PCR (molecular study) evidence of bacteria, culture evidence of bacteria, or both significantly increased the risk of uterine infections and pre-term delivery. 
  • The study also included a correlation with bacterial 16 S rRNA gene copy number, which also, when elevated, was correlated with earlier gestational age, meaning pre-term birth.
  • A negative amniotic fluid culture with a positive PCR for bacteria was associated with a lower mean birthweight and higher amounts of respiratory distress and necrotizing enterocolitis (infected dead bowel) in neonates. This shows the power of PCR analysis relative to culture.
  • The key findings in pre-term deliveries from this are: (1) Microbial Invasion of the amniotic cavity (MIAC) affected half of all those with pre-term delivery, yet this was frequently missed by regular culture results (2) diverse microbes cause pre-term birth. Many of the bacteria were from new phyla and have not been cultivated before. (3) Some of the invasion is a result of gastrointestinal microbes (4) Candida yeast infection was also present more frequently in premature delivery than in prior studies, specially when an IUD had been used. (5) The more microbial DNA  present, the earlier the delivery (6) The fetus has an inflammatory response to the infection reflected in IL-6 and WBC counts in the amniotic fluid, (7) Culture of the amniotic fluid demonstrates infection 34% of the time in pre-term delivery, whereas PCR detects bacterial invasion 50% of the time in pre-term delivery.
  • This is the first study to  demonstrate gastrointestinal tract bacteria as a source of microbes in amniotic fluid.
  • PCR also detected a periodontal source of infection, which was a TM7 member of bacteria that is associated with peridontitis (dental gum infection) and bacterial vaginosis (vaginal infection)
  • The study goes on to identify three Taxa of bacteria that they identified as being associated with pre-term delivery: (1) Atopobium sp, DIalister sp, and Peptoniphilus sp. which cause bacterial vaginosis, an infection associated with premature rupture of the membranes (2) A taxa associated with oral cavity bacteria, which include Filifactor alocis (endodontic infections) and Rothia dentocariosa (associated with odontogenic abscesses and fetal death) In other words, BAD TEETH may be leading to poor fetal outcomes and premature delivery. (3) Myroides spp implicated in urogenital disease and endocarditis. Also noted is that Candida infection (yeast), especially in the setting of an IUD (intrauterine device) is associated with premature birth due to biofilm formation.
  • Bottom line: Positive PCR for bacteria in amniotic fluid is associated with earlier birth rates. Elevated levels of amniotic fluid of bacterial rDNA is also associated with premature delivery.  Higher levels of fetal IL-6 and histological inflammation of fetal membranes is also associated with pre-term delivery. This particular study demonstrated that prior MIAC cases may have been misclassified as being free of microbia invasion or being monomicrobial, when in fact they were not.

 

The vaginal microbiome during pregnancy and the postpartum period in a European population

The vaginal microbiome during pregnancy and the postpartum period in a European population

The abstract of the Nature article is below:

The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n 5 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes

The microbiome in the vaginal area has  bacteria that are believed to inhibit pathogen growth through secretion of antibacterial bacteriocins as well as the production of metabolites such as lactic acid that help to maintain a low, hostile pH6 . Dysbiosis of the vaginal microbiome is associated with complications of pregnancy, in particular an increased risk of preterm birth. The maternal vaginal microbiome may also be an important source of pioneer bacteria for the neonatal gut microbiome.  

In asymptomatic non-pregnant North American women of reproductive age, five vaginal bacterial community state types (CSTs) have been defined. Four of these are dominated by Lactobacillus species including L. crispatus (CST I), L. gasseri (CST II), L. iners (CST III), and L. jensenii (CST V). CST IV is typically characterised by low levels of Lactobacillus spp. and increased diversity of anaerobic bacteria including Prevotella, Dialister, Atopobium vaginae, Gardnerella vaginalis, Megasphaera, Peptoniphilus, Sneathia, Finegoldia, and Mobiluncus. The latter species are often associated with bacterial vaginosis, a clinical syndrome of vaginal discharge and odour characterised by polymicrobial overgrowth, which is linked to an increased risk of preterm birth, and histological chorioamnionitis. Interestingly, in American populations, vaginal bacterial communities dominated by Lactobacillus spp. (CST I, II, III and V) are most frequently observed in Asian and White women whereas a diverse microbiome (CST IV) is more frequently observed in Black and Hispanic populations suggesting that the composition of the vaginal microbiome may be, in part, shaped by genetic differences between hosts but cultural and behavioural factors cannot be excluded to explain these associations.These findings have been recently confirmed and extended by Fettweis and colleagues who identified clear ethnic related differences in the vaginal microbiome of a large population of healthy Black and White Northern American women

The above is part if Nature’s article.

  • Lactobacillus plays a role in keeping the microbiome acidic and stable during a pregnancy. Apparently estrogen levels rise through placental production and this results in the growth of Lactobacillus through increased glycogen stores in the vagina. This glycogen is broken down by alpha amylose into maltose, maltotriose, and maltotetraose, which all support Lactobacillus. After pregnancy, estrogen drops rapidly and so does Lactobacillus. Of note, endometritis ( a uterine infection ) occurs more commonly at this time.  ” Culture based methods have shown early postpartum endometritis is typically characterized by the presence of multiple microbiota often associated with bacterial vaginosis including Gardnerella vaginalis, Peptococcus spp., Bacteroides spp., Staphylococcus epidermidis, Streptococcus agalactiae and Ureaplasma urealyticum.
  • In the Nature article above, it was noted that there are geographical and ethnic differences in the vaginal microbiomes during pregnancy, and that needs to be accounted for in studies.  For example, it was noted that women with a L. gasseri dominated microbiome had the fastest HPV remission rate whereas those with reduced Lactobacillus spp. and increased Atopobium had the slowest remission rate during pregnancy.
  • The bottom line is that during pregnancy, the vaginal microbiome becomes less diverse and more stable with Lactobacillus, but the actual population of Lactobacillus varies by the ethnicity and background of the person.

Preterm birth, intrauterine infection, and fetal inflammation.

Why is understanding the microbiome, even in a crazy place like the vagina so important? Because,  complications of prematurity account for 29% of global neonatal deaths (approximately 1 million) each year and 3.1% of total disability adjusted life years in the global burden of disease. Of course a variety of causes of prematurity exist such as uteroplacental ischemia, cervical disease, decidual hemorrhage, and stress. Evidence is accumulating that both labor and pre-term labor are initiated by a cascade of pro-inflammatory changes. Labor-associated inflammatory changes are characterized by immunocyte infiltration and significant increases in the expression of interleukin (IL)-1β, IL- 6, IL-8, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α expression in the fetal membranes, cervix, amniotic fluid, and placenta

Expression of pro-inflammatory mediators is, in turn, hypothesized to result in (i) increases in prostaglandins, which promote uterine contractility; (ii) degradation of the chorioamnion extracellular matrix; and (iii) ripening of the cervix by matrix metalloproteinases and reduced expression of tissue metalloproteinase inhibitors

With the average American eating over 120 pounds of sugar a year, dental caries are a significant source of infection and inflammation. In part, dental health is associated with birth outcomes – poor teeth causes infection and inflammation that may be associated with pre-term delivery.

 

Complement regulators and inhibitory proteins Complement pathway review

Accessory molecules for Toll-like receptors and their function Toll like receptor review

NOD proteins: regulators of inflammation in health and disease  NOD protein review

Defensins in innate immunity Defensins review

Defensins review

Defensins: antimicrobial peptides of innate immunity

Beyond pattern recognition: five immune checkpoints for scaling the microbial threat