Gut Microbiota for Health World Summit 2019

Diet and the gut microbiome

Diet is a key element for the symbiotic interactions between gut microbes and the host, and it is considered as one of the main drivers in shaping the gut microbiota across lifetime, as reviewed by Jack A. Gilbert (UC, San Diego), Susan Devkota (Cedars-Sinai, Los Angeles), and Lipping Zhao (Rutgers, New Jersey). Foods deliver numerous substrates for microbial metabolism and the microbiome is a chemical factory that synthesizes metabolites important for human health. Macro- and micronutrients in food influence the structure and functions of the gut microbial ecosystem in such way that diet appears to be the most important determinant of similarity in gut microbial composition across humans.[1]

Self-reported dietary data from the American Gut project [2] suggest that the number of unique plant species that a subject consumes is associated with microbial diversity, rather than self-reported categories such as “vegan” or “omnivore”. Higher microbial diversity and higher abundance of short chain fatty acid (SCFA) producer species was found in individuals eating more than 30 types of plants per week as compared to those eating less than 10 types of plants per week. The faecal metabolome also differed between both groups. In addition, individuals who consume more than 30 types of plants compared to those who consume 10 or fewer plants had significantly lower abundance of antibiotic resistance genes.

Dysbiosis of the gut microbiome is a definable state with mechanistic implications. It is not just a change in microbial diversity but a rupture of the mutualistic balance between microbiota and host, where inadequate diet plays a detrimental role. During homeostasis, colonocyte metabolism is directed towards oxidative phosphorylation, resulting in high epithelial oxygen consumption. The consequent epithelial hypoxia helps maintain a microbial community dominated by obligate anaerobes, which provide benefit by converting fibre into fermentation products (SCFA) absorbed by the host. Conditions that alter metabolism of the epithelium, such as a fibre poor diet, increase epithelial oxygenation, thereby driving an expansion of facultative anaerobes, a hallmark of dysbiosis in the colon.[3] The shift in the colonic microbiota composition from obligate to facultative anaerobes, associated with many chronic human illnesses, might have a common underpinning in colonocyte dysfunction. As highlighted by Susan Devkota, if choosing a strict or extreme dietary regime, consuming mixed fibre types can support the microbiome and prevent nutrient deficiencies.

The "Foundation Guild"

Lipping Zhao pointed out that our ancestors had much higher intake of dietary fibres than current consumption rates. Reduced intake of fibres and diminished prevalence of SCFA-producing bacteria may underlie many chronic diseases such as type 2 diabetes. In a randomised controlled intervention trial with Chinese type 2 diabetes patients,[4] high intake of diverse dietary fibres (WTP diet) selectively promoted abundance of a group of acetic and butyric acid producer strains in the gut. The WTP diet is based on wholegrains, traditional Chinese medicinal foods and prebiotics. The WTP diet improved glucose homeostasis by reducing glycated haemoglobin, fasting blood glucose and meal tolerance test.

Abundance of the SCFA producers in faeces correlated with the metabolic outcomes and the blood levels of glucagon- like peptide-1 and peptide YY, which induce insulin secretion. Moreover, reduction of faecal pH by SCFA production correlated with inhibition of detrimental bacteria that promote inflammation and suppress glucagon-like peptide-1 production. In addition to providing SCFAs to directly benefit the host, this group of SCFA producers played important ecological functions in the gut microbiota. Lipping Zhao suggested that they work as the “foundation guild” for structuring the healthy gut microbiota. To help patients regain a healthy gut microbiota, “this foundation guild must be re-seeded and re-established”, he said.

FODMAPS and IBS

As reviewed by Magnus Simren (University of Gothenburg), the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) diet is now being recommended by up to 85% of doctors to treat functional abdominal symptoms. Clinical trials suggest that some patients have a short-term favourable response to a low FODMAP diet, but whether this dietary advice is clearly better than the first line dietary therapy for IBS is uncertain. Of concern, short-term use of the low FODMAP diet has been associated with potentially unfavourable changes in gut microbiota composition, including reduction of fermentative species (Bifidobacterium, Faecalibacterium and Clostridium cluster XIVa) and increased dysbiotic index scores.[5]

A randomized controlled trial compared effects of the low FODMAP diet or the prebiotic GOS on gut microbiota composition.[6] Changes in faecal microbiota differed between both groups after a 4-week treatment period, particularly in relation to bifidobacteria (increase in the prebiotic group and decrease in the low FODMAP group) and Bilophila wadsworthia (the opposite pattern). Despite distinct effects on microbiota, reductions of symptoms were very similar in both groups. Of interest, the decrease in symptoms persisted during the 2-week follow-up after cessation of prebiotic intake, but reappeared immediately after discontinuation the low FODMAP diet. Modulation of gut microbiota as a treatment strategy for IBS seems promising, but long-term safety aspects need to be taken into account. Diets that reduce symptoms but deteriorate gut health (and general health in the long term) should not be the first choice.

Symbiotic trial to prevent newborn sepsis 

Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. Pinaki Panigrahi presented an intervention study to prevent sepsis among infants in rural India.[7] An oral symbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) significantly reduced sepsis and death in newborns (risk ratio 0.60, 95% confidence interval 0.48–0.74). This finding suggests that a large proportion of neonatal sepsis in developing countries could be effectively prevented using probiotic- prebiotic treatment.