Guild level response of human gut microbiome in mitigating oxygen-induced dysbiosis via dietary fibers and elemental iron
Creators: name: Gong, Yongjia
Publisher: name: No Publisher Supplied
Year: 2024

description: The human gut is predominantly inhabited by obligate anaerobic bacteria, maintaining a hypoxic environment. An increased ratio of facultative to obligate anaerobes indicates gut microbiome dysbiosis, associated with a range of chronic conditions including metabolic syndromes and inflammatory bowel diseases. Dietary fibers mitigate dysbiosis by producing short-chain fatty acids (SCFAs), regulating glucose homeostasis, and suppressing facultative anaerobic bacteria. Different processing methods alter the structure and fermentability of dietary fibers, shaping the microbiome accordingly. Antioxidants such as polyphenol and vitamin E also alleviate dysbiosis induced by oxidative stress. However, most studies targeting the relationships between food components and the gut microbiome use taxon-based analysis, which is limited by what is available in the database as well as resolution for differentiating signal from noise. In this study, guild-based analysis was applied to understand the food-microbiome relationship.In chapter 1, we investigated the fermentability of dietary fibers with different processing methods. The raw oats and pinto beans were canned, boiled, extruded with high or low temperature, and introduced in the in vitro gut microbiome fermentation system after in vitro digestion. We hypothesized that different processing methods may alter the fiber structures. Bacteria harboring certain CAZymes may utilize fibers with various structures and proliferate, changing the whole microbiome. Results showed that materials and processing methods both influence the gas production and SCFA generation of gut microbiome. Guild-based analysis found that co-abundance group (CAG) containing facultative anaerobic bacteria such as Escherichia-Shigella ASV0010 were promoted in extruded oats, while CAG containing SCFA producers were significantly promoted in canned and high-temperature extruded pinto beans. This study illustrated that the fermentability of dietary fibers can be affected by processing methods. Therefore, when developing gut microbiota-targeted food, the effects of processing methods on fermentability need to be considered.In chapter 2, we investigated if dietary fibers protect gut microbiome from oxygen-induced dysbiosis. In vitro fermentations utilizing human fecal samples were set up: Control (no oxygen, no fibers), Oxygen (oxygen, no fibers), Fiber (no oxygen, fibers), and Oxygen_Fiber (oxygen, fibers). The hypothesis was that a fiber formula with various dietary fibers can reverse the oxygen-induced disruption of gut microbiota by promoting the growth of anaerobic beneficial bacteria as a preferred energy source, generating SCFAs and lowering pH to repress detrimental bacteria. Results showed that microbiome structure shifted significantly with the introduction of oxygen, which was mitigated by dietary fibers. The Fiber and Oxygen_Fiber groups had lower pH levels and significantly higher SCFA production compared to the Oxygen group. Guilds with facultative anaerobes such as Escherichia-Shigella ASV0010 and Enterobacteriaceae ASV01P9 were significantly proliferated by oxygen but reduced following fiber treatment. In contrast, guilds with potential SCFA producers like Eubacterium ruminantium_ASV00LH were restored by fiber treatment under microaerobic conditions. The study suggested that dietary fibers can safeguard the gut microbiome from oxygen disruption, indicating a potential host-independent beneficial modulatory mechanism of dietary fibers on the gut microbiome.In chapter 3, elemental iron was introduced to investigate its protective effect against oxygen-induced dysbiosis. The hypothesis was that elemental iron might alleviate dysbiosis in gut microbiota by scavenging oxygen and its derivatives. It was found that elemental iron partially reversed the oxygen-induced disruption of the gut microbiota. Inter-individual differences, corresponding to iron oxidation patterns, were observed for the tested donors. Guild with Escherichia-Shigella ASV0010 was promoted by oxygen and depressed by elemental iron, while guilds including bacteria such as Bifidobacterium ASV001D, Blautia ASV054R, were reversed by iron_oxygen treatment. SCFA production was inhibited by oxygen, which was partially reversed by elemental iron. These results suggest that elemental iron can partially regulate the oxygen/ROS state and protect the gut microbiota from oxidative stress.Overall, this thesis illustrates that oxygen-induced dysbiosis can be alleviated by dietary fibers and elemental iron independent of host. Integrating the results from all three studies, key bacteria responding to oxygen and diet factors were identified by guild-based analysis. Some bacteria such as Escherichia-Shigella ASV0010 and Bifidobacterium ASV001D are common responders across different test donors. These bacteria are potential key players in developing microbiome-targeting food and require isolation and characterization in the future.