The effect of combinatory dietary fibers on the gut microbiota and human gastrointestinal health
Creators: name: Wang, Ying
Publisher: name: No Publisher Supplied
Year: 2022

description: Dysbiotic gut microbiome with the overgrowth of pathogenic bacteria have been found to be correlated with gut diseases such as irritable bowel syndrome, inflammatory bowel disease, as well as diseases in distant organs such as obesity, type 2 diabetes (T2DM), acute COVID-19 infection and post-acute COVID-19 syndrome. The inclusion of dietary fibers with diverse physical-chemical structures in a high fiber diet (WTP) consisting of whole grains, traditional Chinese medicinal foods including Fagopyrum tataricum, adlay (Coix lachrymal-jobi L.), yam, peanut, bitter melon (Momordica charantia) and lotus seed, and prebiotics alleviated diseases such as T2DM by selectively promoting a guild of short chain fatty acids (SCFA)-producing gut bacteria and suppressing pathogens such as endotoxin producers. Based on the carbohydrate-active enzyme genes of this guild of SCFA-producing bacteria, one high fiber formula with selected ingredients was designed to resemble the WTP diet. The high fiber formula was tested in an in vitro fermentation system for its effect on modulating gut microbiome and metabolites profile with stool samples collected from T2DM patients and healthy subjects. The formula increased the production of acetic, propionic and butyric acid regardless of the disease status of the subjects and resembled the gut microbiota modulating effect of WTP diet. It changed the microbial metabolites profile of T2DM subjects to become similar to that of the healthy subjects. Eight key bacterial groups that responded to the high fiber formula intervention and that also were associated with disease status were identified as co-abundance groups (CAGs) with 3 potential SCFA-producing CAGs being increased and 5 potential pathogenic CAGs being decreased by the formula. Four CAGs were found to respond differently to the high fiber formula between healthy and T2DM subjects. Each CAG consisted of members from widely different taxa. This indicates that the gut microbiota responds to combinatory fiber treatment as potential guilds rather than taxonomic groups. Selective promotion of SCFA-producing guilds may reduce gut dysbiosis and change the functionality of the patients’ gut microbiota to be similar to that of healthy controls. The high fiber formula was further tested on alleviating severe gastrointestinal symptoms in a single patient with post-acute COVID-19 syndrome. The high fiber formula intervention was found to be associated with the alleviation of severe gastrointestinal and other symptoms. The symptoms severity was found to be significantly associated with the increase of 5 SCFA-producing bacterial ASVs and the decrease of 1 potential detrimental bacterial ASV. In vitro fermentation was also performed on the fecal sample collected from the patient. Similar changes in the gut microbiome were found between samples after 6-12 hours of in vitro fermentation and samples after 2 months of in vivo intervention. This indicates the potential of in vitro fermentation with a short turnaround time to predict the microbiome change of in vivo dietary intervention. To increase the sensitivity of detecting dietary fiber induced changes of gut microbiota in the early stages of the in vitro fermentation, the lysing condition from a recommended DNA extraction method was optimized to achieve saturated lysis of different cells by combining lysozyme pretreatment with chemical and mechanical treatments. Optimization of the lysing condition achieved saturated cell lysing as evidenced by plateaued DNA yield, Gram-positive bacteria ratio in whole microbiome community, and stabilized patterns in beta diversity. With the optimized lysing condition, differences in microbiome structures between early-stage in vitro fermentation samples with three different fiber treatments were detected, where a commercial DNA extraction kit failed to detect any. Overall, my research revealed that 1) the high fiber formula may modulate the microbiome into a healthier state to reduce the differences in metabolites profile between healthy and T2DM subjects; 2) the high fiber formula may alleviate GI symptoms of post-acute COVID-19 syndrome and potentially other functional GI disorders via promotion of SCFA-producing bacteria; 3) higher sensitivity of microbiome analysis may be achieved by combining lysozyme pretreatment with chemical and mechanical lysing during DNA extraction.