Exploring the microbiota of the gastrointestinal tract

Abstract

Abstract: Balanced microbiota of the gastrointestinal (GI) tract is important for maintaining health of the host. Altered gut microbiota have been found to be associated with various life-style induced and other intestinal inflammatory diseases. Gut microbiota is viewed as a metabolic organ and considered as new target for therapies. This thesis describes the work on exploring the microbiota of the GI tract under different conditions. Under the functional food concept, probiotics, prebiotics, food component with prebiotic potientials were used as means to modulate the microbiota of the GI tract. Murine models are commonly used to study the role of the microbiota. However, difference in genetic backgrounds, husbandry conditions may affect the microbiota composition and contribute to the different outcomes of a dietary intervention. We observed that two substrains of C57BL/6 mice fed the same diet harbored different microbiota. In agreement with other studies, this indicates that not only diet but other environmental factors are involved in shaping the gut microbiota. We have investigated the impact of high fat diet on the microbiota and tested multiple functional foods with the aim of improving the host health conditions. We found that high fat diet reshaped the gut microbiota using a mouse model. For example, Allobaculum-like bacteria was decreasing whereas Akkermansia-like bacteria were increasing with high fat feeding in C57BL/6 mice. Supplementations of green tea and Lactobacillus plantarum HEAL19 attenuated high fat-induced inflammation and altered the gut microbiota composition. Combining the L. plantarum HEAL19 with different doses of green tea resulted in a gradient shift in the microbiota and different impact on certain bacterial species. Addition of the dietary fibers i.e. pectin or guar gum shifted the gut microbiota differently. Pectin fed rats had significant reduction in weight gain and had increased abundance of Lachnospiraceae and an unidentified bacterial group. Berries alone or with probiotics were tested under different host health conditions including healthy, hypertensive and inflammatory state. In murine models, raspberry increased bacterial diversity in the microbiota of rats when compared to blackcurrant. The addition of the L. plantarum HEAL19 to the berries did not induce profound effect on the gut microbiota. Fermented bilberries by the L. plantraum HEAL19 showed blood pressure lowering effect in healthy and L-NAME-induced hypertensive rats and altered the gut microbiota composition. Supplementation of bilberries protected against inflammation and oxidative stress in an ischemia−reperfusion-mice model and altered cecal microbiota. The addition of probiotics did not have a profound effect on either the health improvement or gut microbiota composition. Three-month intake of dietary supplements containing either L. plantarum HEAL19 or L. plantarum HEAL19 plus fermented bilberries did not have an obvious impact on the oral and fecal microbiota of hypertensive research persons. Both the oral and the fecal microbiota were relatively stable and the two most fluctuating bacterial taxa in the fecal microbiota were Bacteroides and unclassified Rikenellaceae. In a dextran sodium sulfate (DSS)-induced colitis mouse model, colonic mucosa associated microbiota were different from the healthy controls. Total load of bacteria and the amount of Akkermansia and Desulfovibrio were significantly higher in the mice with colitis than the healty controls. In contrast Lactobacillus was significantly reduced in colitis group. Moreover, the prevelence of Enterobacteraiceae was significantly higher in the colitis group. Ileal pouch microbiota of former patients with ulcerative colitis one year after surgery was colonized predominantly with Fimicutes at phylum level. The most abundant genera during the first year after surgery were found to be Clostridium, Blautia, Roseburia, Lachnospira, unclassified Lachnospiraceae, Bacteroides, Faecalibacterium, unclassified Petostreptococcaceae and Megamonas. In conclusion, diet and other environmental factors are involved in shaping the microbiota of the GI tract. Different diet components have different influence on the microbiota composition. In general, the intestinal Bacteroidales taxa were the most active responders for the diet treatments.

Abstract (Swedish)

Popular Abstract in English

Like earth is home for us, our gastrointestinal (GI) tract is home for microbes. All the bacteria that are living there are called “microbiota” and the total DNA they contain is called “microbiome”. The GI microbiota outnumbers human cells by factor of ten and the microbiome is at least 100 times larger than our human genome. A wide range of metabolic activities are performed by our gut microbiota, such as aid digestion by degrading dietary fibers into smaller nutrients which can be absorbed by our intestinal cells, synthesize vitamins, and educating our immune system. Thus, a balanced GI microbiota is important for maintaining health. An extensive research have shown that an altered GI microbiota is associated with obesity, type 2 diabetes, inflammatory bowel diseases and other illnesses. This thesis describes the work on exploring the GI microbiota under different conditions.

We studied the response of the microbiota to high fat diet and inflammation. In order to guide the microbiota to promote health, we used multiple food or food components such as probiotic bacteria (beneficial bacteria, such as those in yogurt), fibers, oat, green tea leaves and berries. Much of the work has been done on animal models.

When we fed oat containing diet to two types of genetically related mice, only one type of mice showed lowered cholesterol. At the same time these mice had a different microbiota composition. It showed that not only the diet but also other environmental factors are involved in shaping the gut microbiota. It also indicates that the microbiota composition may contribute to the different outcomes of a dietary intervention.

High fat diet changed gut microbiota composition dramatically in mice. Supplementations of green tea and probiotic bacteria (a strain of Lactobacillus plantarum) to a high fat diet re-shaped the microbiota and attenuated inflammation. A higher diversity is often found in a balanced and healthy ecosystem. We found that probiotic bacteria together with lower amount of green tea increased the microbiota diversity (i.e. the number of different species of bacteria) to a high degree; whilst with higher amount of green tea the Gram negative (bacteria with a certain cell wall structure) of the family Enterobacteriaceae (comprising many harmful bacteria) was reduced.

Addition of dietary fibers such as pectin or guar gum induced different responses of the gut microbiota. Interestingly, pectin fed rats had a significant reduction in weight gain and had increased number of certain bacteria including those that can degrade pectin.

Different berries had different influences on the gut microbiota as well. Raspberry increased diversity of the microbiota when compared to blackcurrant, while addition of the probiotic strain L. plantarum HEAL19 to the berries did not show any profound effect. Bilberries (European blueberry) fermented by lactobacilli showed blood pressure lowering effect in healthy and hypertensive rats and altered the gut microbiota compostion. Moreover, bilberries showed protective effect against inflammation and oxidative stress and altered the gut microbiota in mice. The addition of probiotic bacteria did not result in a profound effect on either the health improvement or gut microbiota compostion. Three-month intake of dietary supplements containing probiotic bacteria or bilberries fermented with the same bacteria did not have an obvious impact on the oral and fecal microbiota of individuals with high blood pressure. Both the oral and the fecal microbiota were relatively stable, while two groups of bacteria in the feces varied in numbers by time. Those bacteria were Bacteroides and members belonging to unclassified Rikenellaceae.

In a mice model mimicking human ulcerative colitis, the microbiota associated to the colonic mucosa were different from that of healthy ones. The total load of bacteria, the amount of the two bacterial genera Akkermansia and Desulfovibrio and the prevelance of Enterobacteraiceae (all of these three are Gram negative bacteria and might be considered as less healthy ones) were significantly higher in the mice with inflammation in colon than in the healthy ones. In contrast, health promoting Lactobacillus was significantly reduced in group with inflammation in colon. The mucosa of ileal pouch (that is a pouch that the surgeon makes from a part of the small intestine to replace a colon that has been removed) from former patients with ulcerative colitis one year after surgery was colonized predominantly with a division of bacteria called Fimicutes but also bacteria that have been seen in connection to ulcerative colitis were present in some patients.

In conclusion, diet and other environmental factors are involved in shaping the microbiota of the GI tract. Different diet components have different influences on the microbiota composition, which affects our health. Dietary interventions may exert health promoting effects by guiding the microbiota to develop towards a more balanced and healthy ecosystem.

• author: Xu, Jie
• supervisor: Göran Molin
• opponent: Dr. Scott, Karen, Rowett Institute of Nutrition and Health, University of Aberdeen, United Kingdom
• organization: Division of Food and Pharma
• publishing date: 2014
• type: Thesis
• publication status: published
• subject: Nutrition and Dietetics
• keywords: Microbiota, Probiotics, Blood pressure, High fat diet, Oat, Green tea, Berry, Fiber, Exopolysaccharides, Ulcerative colitis
• pages: 140 pages
• defense location: Lecture Hall F at the Center for Chemistry and Chemical Engineering,Getingevägen 60, Lund University Faculty of Engineering.
• defense date: 2014-01-24 13:15:00
• ISBN: 978-91-7422-339-2
• language: English
• LU publication?: yes
• additional info: The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Applied Nutrition and Food Chemistry (011001300)
• id: eefb50a6-93ad-47f8-9367-8c1de15c536b (old id 4216132)
• date added to LUP: 2016-04-04 11:06:18
• date last changed: 2018-11-21 21:02:41