The Human Gut Microbiota Part 3

NUTRITION & SUPPLEMENTATION

THE HUMAN GUT MICROBIOTA THE COMPOSITION OF THE HUMAN GUT MICROBIOTA - PART THREE

Written by ACA Contributor Andrew Chappell BSc (Hons), MSc, PhD, RNutr Sport

As previously stated the complexity and number of bacteria that inhabit the GIT increases with progression down the GIT from the small intestine to the large intestine (Figure 12). The continual supply of nutrients delivered to the large intestine and fairly consistent pH makes the GIT a perfect environment for gut microbes (Moore & Holdeman 1974, and Finegold et al. 1977). Advances in genome sequencing technologies, combined with the reduction in cost of these technologies, has meant our understanding of the bacteria that inhabit the human GIT has increased significantly over the past 20 years (Zoetendal et al. 2008). The microbiota is relatively stable throughout adult life, with the exception of disease states, although a certain degree of fluctuation is possible with antibiotic treatment, infections and changes in dietary patterns (Duncan et al. 2007, David et al. 2014a, and David et al. 2014b). In infancy the microbiota seems to be less complex and is dominated by species belonging to the Actinobacteria phylum predominantly Bifidobacteria spp. commonly sold as probiotics, and similarly as we age and become infirm there may be a tendency towards a less diverse microbiota (Penders et al. 2007 and Claesson et al. 2012).

Increased understanding has resulted in a renaissance in research categorising the microbiota. Previously researchers could only study microbes that they could grow in the lab; this meant that Bifidobacterium and Lactobacillus were disproportionately studied. Moreover, for a long period of time one, Firmicutes one of the major phylum (which can make up to 50 % of a person's microbiota) went unstudied until the late 80s. The result of all this means that prior to the 1990's there was considerable focus placed on the easily grown probiotic species Lactobacillus and Bifidobacterium which make up relatively small proportions (<0.5% and 1% respectively) of the colonic microbiota in the healthy adult (with Lactobacilli undetected in the previous Italian and Hadza examples) by comparison to far more abundant microbes like Faecalibacterium prausnitzii (up to 9%). This has resulted in a lasting legacy whereby the Lactobacillus and Bifidobacterium have been prescribed as cure all's and go to probiotics for all ailments of the gut despite a lack of efficacy and the removal of probiotic status by the European Food Safety Authority.

Figure 12. Summary of the most prevalent microbes occupying different regions along the Gastrointestinal Tract: TM7 (candidate division). Taken from Brown et al. (2013).

The Healthy Adult Microbiota

The four main phyla found within the healthy adult make up to 95.5 % of all bacterium found within the gut (Ley et al. 2008, DeFilippo et al. 2010, and Schnorr et al. 2014). The remaining bacteria that populate the gut belong to the Cyanobacteria, Fusobacteria, Spirochaeta, Fibrobacteres and Verrucomicrobia phyla, with much lower and variable proportions and abundances. It was previously thought that the ratio of Firmicutes and Bacteroidetes may have important consequences for health, however data from large scale projects like the HMP have demonstrates that the ratio within a cohort of healthy volunteers can vary between 95:5 to 5:95 % in favour of either phyla. This suggesting that even within the healthy state the microbiota can occupy a range of configurations (Figure 13) (The HMPC 2012). Interestingly despite the range of configurations there is considerable similarity in the metabolic potential of those microbes. Or in other words the microbes perform similar roles despite their difference in composition if you recall the ecosystem example I gave previously.

Figure 13. Diversity of the human microbiota from sites around the body. Panel A reflects different bacterial phyla at seven different sites around the body. Anterior nares (nostrils), RC, retroauricular crease (behind ears) Buccal mucosa (cheek), supra- and subgingival dental plaque (tooth biofilm above and below the gum), Tongue dorsum (tongue soft tissues), Stool (colon microbiota), posterior fornix (vaginal sample). Panel B refers to the metabolic capability of the microbial population.

Firmicutes belonging to the butyrate producing Lachnospiraceae and Ruminococcaceae Genus have been shown to make up to 35.5 % of all bacterial counts from healthy human faecal samples (Chassard et al. 2008). Within these clusters, bacteria belonging to the Roseburia genus and F. prausnitzii species comprised as much as 8.9 and 12.2 % of all bacteria while Bacteroides-Prevotella, Actinobacteria and Negativicutes make up 15.1, 5.1 and 9.9 % of counts respectively Chassard et al. (2008), at least in Western populations. Below the genus level, the microbiota becomes harder to classify, due in part to the large number of different species present within and individual (Qin et al. 2010). Despite difficults in characterising beyond species bacteria recovered from faecal samples show 18 species to be present in at least 57 % of individuals and 75 species in 50 % of individuals which suggests some form of common core as mentioned earlier (Qin et al. 2010). However even for the 57 most common species present in over 90 % of individuals their abundance ranged 12 to 2,187 fold between individuals. Or in other words a person may possess a common microbe, but that microbe may play a significant role in one person and an insignificant in another.

Another way the gut microbiota can be considered is as a “communities of genes”. This is perhaps my favourite way to consider the microbiota. This is where different bacteria with similar genetic potential may fill an environmental niche. You therefore look at a person’s genetic richness within the microbiome and it’s potential, rather than trying to determine the gut microbiomes potential by looking at the species. If we look at Human Microbiome Project example we can see variation between subjects in bacteria but, metabolic pathways are ubiquitous (Figure 13b) (The HMPC 2012, and Chantelier et al. 2013). The Hadza vs Italian cohort again provides as with a great example of microbiota potential with the Hadza microbiota more capable of digesting nutrients than Italian microbiota measured by the number of enzymes they possess (Figure 14).

Figure 14. Differences in the number of digestive enzymes possessed by the microbiota between Hadza hunter gathers and Italians. The Black line across the box plot represents the Median number of enzymes, the box corresponds to where 50% of all subjects data points lie. On average the Hadza microbiota is capable of digesting far more different types of carbohydrate than the Italian microbiota.

The presence of bacterial specialists should however not be discounted, and subjects lacking Ruminococcus bromii have been shown to be incapable of degrading type III resistant starch (Xiaolei et al. 2012). Indeed, there is differences in the ability for people to extract energy from fibre across a population as a result. For example, one individual may be able to extract 0 to 1 kcal of energy from a gram of fibre compared to 2 or 4 kcal in a different individual. There does appear to be few truly keystone species eve Bifidobacteria who had previously thought to be the sole target of prebiotic compounds inulin and fructo-oligosaccharides is not immune with many gut microbes beyond the Bifids seemingly capable of fermenting these prebiotics. Interestingly microbial genes and thus microbial richness may negatively correlate with disease. In experiments where healthy weight individuals have been compared to obese subject’s higher numbers of genes have been counted in the healthy weight individuals compared to the obese individuals. This

indicates that those with low gene counts were more likely to be obese and have a lower species diversity than non-obese individuals (Chantelier et al. 2013). Those with low gene counts were found to have an increased capacity for potentially deleterious metabolites: β-glucuronide, degradation of aromatic amino’s, nitrate reduction, sulphate producing capacity and lower production of the beneficial SCFAs. There is also the suggestion that there may be an increase in inflammatory molecules such as lipopolysaccharides P (LPS) (drinkers of butter and bulletproof coffee may recognise LPS) and oxidative stress which might contribute towards subsequent N disease of the lower bowel (Chantelier et al. 2013).

The Microbiota in Growth and Development

During birth, the previously sterile GIT is colonised by microbes from the mother’s vagina, faeces (Ardissone et al. 2014). The mode of delivery therefore has a bearing on the early infant microbiota, and infants born by caesareans have microbiotas resembling their surrounding environment compared to one resembling the mother (Dominguez–Bello et al. 2010, Ardissone et al. 2014, and Backhed et al. 2015). Bacterial diversity increases with infant’s age, although those born by caesarean still differ compared to their vaginally born peers at 12 months (Backhed et al. 2015). The developing microbiota is also influenced by whether infants is breast or formula fed (Penders et al. 2007, Boehm & Moro 2008, and Oozeer et al. 2013). Human breast milk is high in oligosaccharides (medium chain carbohydrates) with over 1000 structurally diverse and distinct molecules (Boehm & Moro 2008). Human milk acts like a prebiotics and selectively increases Bifidobacteria in the infant (Bohehm & Moro 2008). Breast milk also contains specialist molecules that interact with the immune system and prevent harmful bacteria from colonising the GIT as well as assisting in the immune systems development (Oozeer et al. 2013). The microbiota of the breast fed infant microbiota is therefore different from that of the formula fed and is dominated by the Actinobacteria phylum of which 75 % of species belonging to the Bifidobacterium genus (Oozeer et al. 2013). Formula fed infants have a more diverse microbiota, but a lower percentage of Bifidobacterium, between 10 and 50 % (Knol et al. 2005, Penders et al. 2007, Oozeer et al. 2013). The formula fed infant microbiota also has higher numbers of pathogenic bacteria including: C. difficile, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Enterobacter and Pseudomonas aeruginosa. Some have suggested that this increased abundance of pathogenic bacteria in the infant may influence the development of atopic diseases (Penders et al. 2007). With the introduction of solid foods by 12 months the signature adult genera: Bacteroides; Clostridiales; Anaerostipes; Clostridium and Roseburia start to appear (Backhed et al. 2015), although by three years of age the composition still does not resemble that of an adult (Yatsunenko et al. 2012).

The Elderly Microbiota

The human adult microbiota is relatively stable with the exception of illness, antibiotic use and changes in diet, however the microbial diversity of the elderly may be reduced (O’Connor et al. 2014). It is unclear if this reduction in diversity corresponds to health status or lifestyle. The effects of diet and frailty on the gut microbiota have been investigated and distinct patterns seem to emerge based on health status and inflammatory markers (Claesson et al. 2012). Frail elderly individuals had higher faecal water concentrations and lower SCFA compared to their healthy peers (Claesson et al. 2012). Diet played a key role in determining the microbial composition of the elderly, with those who consumed a diet high in fibre and low in fat possessing a more diverse microbiota (Claesson et al. 2012). Conversely those who consumed a low fibre, high fat diet had a lower microbial diversity and tended to be frailer. Taken together it is not inconceivable to assume that health status and diet can influence the microbial community of the elderly subject and that diversity may be greater in elderly subjects living in the community. Those subjects who consuming a diet high in grains, fruits and

vegetables whilst being low in fats seem to retain a microbial community more similar to that of a healthy younger subject despite their advanced years. Strategies that aim to increase microbial diversity could therefore be beneficial in promoting healthy aging.

The Inﬂuence of Diet, Geography and Environment on the Microbiota

Comparisons between the microbiota of individual’s resident in different countries, and between twins have shown interesting differences related to diet and geography. Habitual diets of those living in rural Malawi and Venezuela are significantly higher in dietary fibre and lower in meat and processed foods compared to US residents. Adults living rurally in Venezuela and Malawi have greater microbial diversity compared to US residents. Unsurprisingly the microbiotas twins are more similar than unrelated children suggesting a combined role of genetics and shared environment in shaping the microbiota (Yatsunenko et al. 2012).

Diet is therefore an important factor in defining the composition of the microbiota and may explain some of the differences between Western and non-Western microbiotas. The Hadza diet is extremely high in dietary fibre (between 50 and 300 g per day) and the lifestyle resembles that of a Palaeolithic human where they consume a seasonal diet based on five categories: meat, honey, baobab, berries and tubers (Schnorr et al. 2014). Hadza microbiotas are dominated by Firmicutes (72 %), Bacteroidetes (17 %), Proteobacteria and Spirochaetes (3 %), with the most dominant families being the Ruminococcacea (34 %), Lachnospiraceae (10 %), and Prevotellaceae (6 %). Gender microbiota differences are also apparent which is explained by the contrasting roles played in Hazda society. Men spend their time hunting for food and eat more meat and honey, while women forage and consume more tubers and baobab. The Hadza microbiota (Schnorr et al. 2014) is even distinct from the West African samples from Malawi (Yatsunenko et al. 2012) and Burkina Faso (DeFillippo et al. 2010) suggesting a strong influence of the Hadza lifestyle, compared to those in rural West Africa who practice animal husbandry and agronomy.

Detailed analysis of the microbiota by geography also indicates that the Prevotella genus present seen amongst Malawians, Venezuelans, Hadza, and children of Burkino Faso is absent from US adults (De Filippo et al. 2010, Yatsunenko et al. 2012, and Schnorr et al. 2014). Separating the influence of environment and host diet on the microbiota is difficult. Some have suggested the influence of diet may influence microbiota variability between 3 to 20 %, while heritability may account for between 40 to 70 % (Wu et al. 2011, Chantelier et al. 2013). Clearly environment beyond the diet may explain a vast amount of the variation within the microbiota.

The Diet the Microbiota and Colorectal Cancer

Diet and lifestyle is thought to play a key role in shaping the gut microbiota, particularly in the development of colorectal cancer. The current paradigm suggests diet may play a role in its development. Diets high in red and processed meat, while low in fibre, increase the exposure of colon cells (colonocytes) to carcinogenic compounds (heterocyclic amines and nitrosamines) while reducing the exposure to potentially beneficial metabolites like the short chain fatty acid butyrate (Bingham 1990). Prolonged exposure to these diets over a lifetime increase the risk of developing colonic adenocarcinoma (Bingham 1990). Like CVD, a lack of physical activity, obesity, smoking, T2D, and alcohol intake contribute to the disease (Huxley et al. 2013). The gut microbiota is explicitly linked to diet and fibre intake and specific bacteria such as Faecalibacterium prausnitzii and Roseburia species degrade fibre, produce anti- inflammatory metabolites and are known butyrate producers which may be protective against the disease (Sokol et al. 2008, and Cao et al. 2014).

Results from the European Prospective Investigation into Cancer and Nutrition (EPIC), the largest and most comprehensive study carried out to date on diet and cancer, suggest those who consumed a diet high fibre had a reduced risk of developing large bowel cancer. For every 10 g/day of fibre consumed, risk was reduced 0.87% (95 % CI: 0.79-0.96). Interestingly, the inverse relationship is maintained after adjusting for red meat and processed meat (Murphy et al. 2012). The EPIC cohort also provided useful insights into how red rather than white meat may increase the risk of CRC. For every 100 g of red meat consumed daily above the 80 g recommendation, the risk of CRC increased by 1.25%. However a recent meta-analysis suggested previous evidence regarding the role of red meat in CRC development may be overstated, claiming much poorer associations, with a relative risk of 1.1 (95 % CI: 1.03 – 1.19). It is therefore not inconceivable this risk could mitigated by increased intake of fruits, vegetables and wholegrain cereals (Alexander et al. 2015).

The formation of carcinogenic nitrosamine compounds is associated with haem iron intake found in meat, (so no amount of grass fed cattle will mitigate this risk) and lack of fibre may be more important than red meat alone (Holtrop et al. 2012). Indeed some evidence suggests that apparent total n-nitroso compounds formation may be reduced in the presence of a moderate carbohydrate and fibre intake (Silvester et al. 1997, and Holtrop et al. 2012). Epidemiological studies are often cited for their inability to prove causation, however the fact that many of these relationships were maintained despite adjusting for confounders should be regarded as a strength of these studies.

Several mechanisms by which wholegrains and dietary fibre may prevent CRC have been suggested. Indigestible insoluble carbohydrates have laxative effects, increasing faecal wet weight and speeding up intestinal transit (Bingham 1990). The increase in faecal weight and decreased transit time reduces the exposure of the colonocytes to faecal mutagens and carcinogenic compounds like secondary bile salts, ammonia, nitrosamines, p-cresol, apparent total N-nitroso compounds and hetrocyclic amines (Russell et al. 2011). Wholegrains additionally contain vitamins, minerals and phenolic compounds with potential antioxidant properties lost during refining process. Antioxidant compounds such as tocopherol and ferulic acid may inhibit the conversion of less carcinogenic compounds into more carcinogenic nitrosamines at physiologically relevant pH’s (Wattenberg 1985).

Finally, fibre is fermented by the colonic microbiota producing short chain fatty acids (SCFA) which decrease colonic pH and reduce the solubility of secondary bile acids (Ridlon et al. 2006). Conversely high protein, high fat, low carbohydrate and low fibre diets may be detrimental to colonic health as the Colonocytes are exposed to an increased number of carcinogenic compounds (Russell et al. 2011). The level at which carbohydrate or dietary fibre consumption might attenuate the influence of high protein, high fat diets is currently unknown. Comparison of two different diets; a high protein, low carbohydrate diet (29 % protein, 5 % carbohydrate, and 66 % fat), and a high protein, moderate carbohydrate diet (28 % protein, 35 % carbohydrate, and 37 % fat) found that exposure to apparent total n-nitroso compounds was increased significantly in the high protein, low carbohydrate diet, while total SCFAs were reduced (Russell et al. 2011). It would be interesting to compare the effect of a high protein, high carbohydrate and low fat diet on apparent total n- nitroso compounds, to assess if the potential toxicity of protein is reduced in the presence of lower fat and higher carbohydrate intakes. Interestingly a more recent study comparing soya with casein as the main source of protein in a high protein low carbohydrate diet found no difference in bacterial profiles and a reduction in SCFAs in both diets, highlighting the important role carbohydrate plays in colonic health. (Beamont et al. 2017).

The mechanisms by which wholegrains may be protective against CRC may also be mediated through changes in the gut microbiota composition and fermentation products. F. prausnitzii may play a role in IBD remission in part due to its role as butyrate producer (Duncan et al. 2002). Butyrate is the main energy source for colonocytes, it is thought that butyrate consumption near the base of the

luminal crypt causes cell proliferation and stimulates mucus production (Sokol et al. 2008). Excess butyrate superfluous to the colonocytes is absorbed into the nucleus where it can influencing cell proliferation and apoptosis, important regulators of a cells life particularly in cancer (Canani et al. 2011, and Bultman 2014).

Diets high in animal protein and fat result in a microbiota dominated by the Bacteroides and Prevotella compared to the Ruminococcaceae and Lachnospiraceae known plant fibre degraders. Low carbohydrate diets have also been shown to significantly reduce numbers of Bifidobacteria, Ruminococcaceae, Lachnospiraceae and E. rectale (Duncan et al. 2007). Extreme dietary intervention devoid of fibre (< 1 g day) and high in animal protein and fat resulted in an increase in Bacteroidetes, Alphaproteobacteria and Verrucomicrobia (David et al. 2014a). Subsequent analysis by Powers et al. (2014) identified from 10 nutritional studies (7 cross sectional, 2 feeding and 1 randomised control trial) that Bacteroidetes seemed to be associated with a high fat and low fibre based diet, while Firmicutes seemed to correlate more with high fibre intakes. While a dietary intervention study compared a high wholegrain with a red meat diet for three weeks each (Foerster et al. 2014), the diets being isocalorifically matched microbial diversity was increased significantly in the wholegrain group compared to the red meat group (Foerster et al. 2014).

Fibre fermentation is important for the production of SCFA and a diet low in plant based foods corresponds to a drop in SCFA concentrations as well as butyrate producing bacteria (Duncan et al. 2007 and David et al. 2014a). Acetate (a SCFA) is also reduced on such low fibre diets, and the branched chain fatty acids isovalerate and isobutyrate increase along with bile salt and sulphite metabolism in response to the higher intakes of protein and fat (Duncan et al. 2007 and David et al. 2014a). These last few points are generally considered bad for colonic health. A lack of SCFA production results in an increased colonic pH allowing potentially harmful bacteria like Alphaproteobacteria and Proteobacteria to propagate (Duncan et al. 2009 and David et al. 2014a). Previously insoluble carcinogenic molecules like secondary bile salts also become more soluble at the higher pHs in the absence of SCFA production (Ridlon et al. 2006). The changes in the microbial composition and metabolites produced on the animal based diet may contribute to the development of IBD (Ridlon et al. 2006, Russell et al. 2011, and David et al. 2014a). Work in this area is still very much in its infancy, however early signs point to the fact that diets high in animal fat and protein may over a lifetime be detrimental to colonic health.

Probiotics, Faecal Microbial Transplants and Prebiotics

Probiotics

Probiotics are defined by The World Health Organisation as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” (Food and Agricultural Organization of the UN and WHO 2002). Despite this definition some have argued a more precise term maybe useful for consumers and clinicians (Hill et al. 2014). Although making up a relatively small proportion of the adult microbiota the probiotic bacteria Bifidobacteria spp. and Lactobacilli spp. are thought to be potentially beneficial for health (Eckburg et al. 2005, and Walker et al. 2008). The rationale for the use Bifidobacteria perhaps comes from observations that atopic disorders, autoimmune and gut disease are absent in infants where Bifidobacteria make up a larger proportion of the microbiota (Penders et al. 2006). While Eli Metchnikoff made the link between fermented milk containing Lactobacillus longevity and “toxic gut” in the early 20th century (Brown and Valiere 2004). Since then there has been considerable

interest in probiotics and many are commercially available, although currently no health claims associated with these products are endorsed by EFSA and only bacteria with approved health claims can be described as probiotics (Binnendijk and Rijkers et al. 2013).

Despite the lack of approved health claims, research in this area is considerable and ranges from studies investigating GIT diseases and infections, to atopic disorders and cosmetic skin treatment. Research however has been somewhat conflicting, for example, some have reported that the current range of probiotics may only be effective in specific disease states such as: necrotizing enterocolitis in pre-term infants; antibiotic associated diarrhoea, acute infectious diarrhoea and the remission maintenance of pouchitis after ileal pouch anastomosis (Bron et al. 2011). Conversely, others have reported probiotics were generally beneficial in the treatment and prevention of GIT disease but were ineffective in treating Traveller’s Diarrhoea or necrotizing enterocolitis (Ritchie and Romanuk 2012). One of the challenges in drawing conclusions on the efficacy of probiotics is a lack of studies on individual species or strains. Most meta-analysis group probiotics as treatments rather than species or strains leading to high heterogeneity and an over estimation of effect as stated previously bacteria are individual species and cannot be substituted like for like. Thus more research is needed to determine the true efficacy of individual species and strains in the prevention and treatment of disease before they can become licenced probiotics (Binnendijk and Rijkers et al. 2013). What this means for the average health and fitness professional is that currently the efficacy for the use of probiotics in otherwise healthy populations is undetermined. Although certain microbes can be regarded as keystone and essential in supporting the wider population at this current time there may be more obvious probiotic targets. F. prausnitizii, Roseburia spp. and several Bacteroidetes spp. can make up between 3- 9 % each of a Western individuals microbiota and could be ideal next generation of probiotics.

Prebiotics

Away from using microbes to modulate the microbiota there’s also the potential to use prebiotics. A prebiotic is “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” (Gibson et al. 2010). Unlike probiotics where micro-organism have to compete with established communities, prebiotics seek to modify the microbiota by targeting existing communities. Prebiotic research has largely focused on the probiotic targets Bifidobacteria spp. and Lactobacilli spp. using fructans like inulin, Fructo-oligosaccharides (FOS) and Galacto- oligosaccharides (GOS) (Macfarlane et al. 2008, and Gibson et al. 2010). Although it is worth noting that in the case of prebiotics like inulin and FOS multiple species beyond Bifidobacteria spp. are capable of fermenting these prebiotics including members of the Ruminococcaceae, Lachnospiraceae and Bacteroides families (Scott et al. 2013). Thus any perceived benefit incurred by a prebiotic may be down to changes in the wider microbial community rather than exclusive increases in Bifidobacteria or Lactobacilli. It is also important to consider that once a better ceases taking a prebiotic, the microbiota may likely return to the previous configuration. Thus health and fitness professionals may consider diet to be a more viable long term strategy in order to achieve a balance of healthy SCFA producing bacteria. Research into prebiotics however does not seem to suffer from the same heterogeneity as probiotic and currently EFSA supports the view that inulin consumption over 12 g per day may improve bowel function (Panel on Dietetic Products).

Faecal microbial transplants

The use of defined cultures or faecal microbial transplants (FMT) for C. difficile associated diarrhoea has generated considerable interest (Bakken et al. 2009, Lawley et al. 2012, and Petrof et al. 2013). A defined cultures mix containing six cultured representatives of Lachnospiraceae, Bacilli, Actinobacteria and Bacteroides has been shown to be effective treatment in C. difficile epidemic infected

mice (Lawley et al. 2012). This bacteriotheraphy triggered major shifts in the microbial community structure replacing C. difficile and reduce disease infectiousness (Lawley et al. 2012). Similar work has proven to be extremely effective when carried out in humans with C. difficile infection using thirty-three isolates from a faecal samples in the RePOOPULATE study (yes they really called it that!) (Petrof et al. 2013). Faecal microbial transplants have also been shown to be extremely effective and between 1958 and 2008 faecal microbial transplants have a reported a success rate of at least 81 % in curing recurrent C. difficile infections (Bakken et al. 2009). Colonisation resistance is thought to be a one possible explanation for the success whereby the defined culture outcompetes C. difficile and allows the re - establishment of a healthy microbiota. However, don’t be sending away for your favourite celebrities stool just yet, concerns remain however about the possible transmission of pathogens from patients, standardisation of treatment and who should be considered a suitable donor.

The Microbiota and Obesity

Changes in the gut microbiota have been observed in obesity and work carried out in experimental and germ free animals has shown the obese phenotype (the physical manifestation of a genotype) may be transmissible from obese animals to non-obese animals (Turnbaugh et al. 2006). A change in the ratio of Bacteroidetes to Firmicutes in favour of Firmicutes was proposed as an early explanation for the increased energy harvest (Ley et al. 2006 and Turnbaugh et al. 2006) but this was not supported by subsequent work, with others reporting the opposite when obese and overweight individuals were compared to lean controls (Schwiertz et al. 2009). The Firmicutes to Bacteroidetes ratios within a cohort can range from 95:5 to 5:95 dependent on the individual, thus the ratio is in fact too crude to draw any measureable conclusions on the obese microbiota (The HMPC 2012). There are many who also don’t consider animals, let alone germ free animals to be good models for this type of research, since the microbiota they harbour is completely different to that of a human, and germ free animals fail to develop like normal animals. The microbiota contributes up to 10 % of a person’s energy intake (with the bulk of energy coming from nutrient absorption in the upper GIT) it therefore seems impractical that the microbiota could be the cause of obesity in the face of an energy dense nutrient poor diet.

An interesting concept is the idea that the microbes within our gut could be directly driving decision making and food choices. The microbes within our gut can directly interact with nervous tissue responsible for sending signals to the brain. It’s a little bit twilight zone and not as out there as you might think, when you consider how some diseases are transferred in animals. A reduction in the overall community gene count and bacterial diversity however has been reported in obese individuals (Chantelier et al. 2013). This is in much the same way other diseases are characterised by a loss of diversity. Certain microbial species may also be predictors of an individual’s ability to lose weight and modelling studies have shown that a higher abundance of Clostridium sphenoides was correlated with weight loss (Korpela et al. 2014). Christensella minuta has also been reported to be enriched in lean compared to obese individuals in a twin study (Goodrich et al. 2014). Obesity is also a major risk factors in the development of T2D, CVD and NAFLD and is often accompanied by one or more as a comorbidities. This close link between obesity in its comorbidities raises the question is the change in the microbiota simply a consequence of the metabolic syndrome. The idea that the microbiota however is the cause of obesity has however fallen out of fashion in recent years.

Key points, the reader should take from this mini three article review are:

• The microbiota plays a key role in the maintenance of the immune system and development of the gastrointestinal tract

• The microbiota provides the host with energy through the fermentation of nutrients that escape digestion in the upper gastrointestinal tract

• There is huge inter-individual variation in the microbiota, and every person has their own microbial finger print

• Microbial diversity and richness may be important indicators health

• Disease states are characterised by low bacterial diversity and richness rather than specific ratios of Bacteroides to Firmicutes

• The short chain fatty acid metabolites produced through this fermentation are considered beneficial for health and maintain a low pH within the colon

• high protein, high fat diets, increase the amount of carcinogenic compounds delivered to the bowel, reduce bacterial diversity, increase the colonic pH and reduce beneficial SCFA metabolites

• The gut microbiota is susceptible to modulation through the diet, and prebiotics

• Certain bacteria may be beneficial for health in certain populations, only species with proven health benefits can be licenced as probiotics, currently there are no licenced probiotics in Europe.

• Changes in the gut microbiota is unlikely to lead to obesity and changes in its composition is more likely a consequence rather than a cause.

Written by ACA Contributor Andrew Chappell BSc (Hons), MSc, PhD, RNutr Sport

Andrew is a professional natural bodybuilder and has been involved in the health and fitness industry for over 10 years as an instructor, coach, nutritionist, researcher and lecturer. Andrew has an undergraduate degree in sport and exercise science from Herriot Watt University, a post-graduate degree in human nutrition and metabolism from Aberdeen University and PhD in human nutrition from the Rowett Research Institute. During his PhD Andrew studied the effects of dietary fibre on human health, specialising in; the environmental and genetic factors influencing the nutrient composition of cereals, and the effect of dietary fibre on the colonic gut microbiota. Andrew lectures in sports nutrition at Sheffield Hallam University with a current research focus on, the dietary strategies of natural bodybuilding populations and ergogenic aids in resistance training. As a course tutor with ACA he’ll be delivering content with a specific focus on gut health and disease.

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