Image_3_Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.tiff

Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients’ gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.</p

Table_2_Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.xlsx

Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients’ gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.</p

DataSheet_3_Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites.xlsx

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.</p

Table_4_Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.xlsx

Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients’ gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.</p

DataSheet_1_Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites.docx

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.</p

Image_4_Fecal Microbiota Transplantation Donor and Dietary Fiber Intervention Collectively Contribute to Gut Health in a Mouse Model.tiff

Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients’ gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.</p

Table_1_Intermittent Fasting Reshapes the Gut Microbiota and Metabolome and Reduces Weight Gain More Effectively Than Melatonin in Mice.xlsx

Background: Intermittent fasting (IF) can reduce energy intake and body weight (BW). Melatonin has many known functions, which include reducing appetite and preventing excessive weight gain.Objective: This study aimed to investigate the effects of IF on body fat and the gut microbiota and metabolome as well as a potential interaction with melatonin.Methods: Male C57BL/6J mice (23.0 ± 0.9 g, 6 wk old) were randomly assigned into four groups (12 mice/group): control (C), intermittent fasting (F), melatonin (M), and intermittent fasting plus melatonin (MF). The C and M groups mice were provided with ad libitum access to food and water, while the F and MF groups underwent alternative-day feed deprivation (15 cycles total). Melatonin was administered in the drinking water of the M and MF groups. Blood, epididymal fat, liver tissue, and intestinal tissue and contents were collected for lab measurements, histology, and microbiota and metabolome analysis. Main effects and interactions were tested by 2-factor ANOVA.Results: IF significantly reduced BW gain and serum glucose, total cholesterol (TC) and triglyceride (TG) levels. Adipocyte size significantly decreased with IF, then the number of adipocytes per square millimeter significantly increased (P Conclusions: IF, but neither melatonin nor the interaction between IF and melatonin, could alter intestinal microbiota and metabolism and prevent obesity by reducing BW gain, serum glucose, TC, and TG, and adipocyte size in mice.</p

Table_2_Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota.XLS

Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed “non-industrialized” and “industrialized” gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.</p

Table_4_Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota.XLS

Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed “non-industrialized” and “industrialized” gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.</p

DataSheet_4_Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites.xlsx

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.</p