Effects of inactivated Lactobacillus rhamnosus on growth performance, serum indicators, and colonic microbiota and metabolism of weaned piglets.

BACKGROUND: To assess the effects of inactivated Lactobacillus rhamnosus (ILR) on growth performance, serum biochemical indices, colonic microbiota, and metabolomics in weaned piglets, 120 piglets were randomly divided into five groups. Samples in the control group were fed a basal diet, while the experimental ILR1, ILR2, ILR3, and ILR4 groups were fed basal diets supplemented with 0.1%, 0.2%, 0.3%, and 0.4% ILR, respectively. The prefeeding period lasted for 5 days and was followed by a formal period of 28 days. RESULTS: Compared to the control, the average daily gain increased by 4.38%, 7.98%, 19.32%, and 18.80% for ILR1, ILR2, ILR3, and ILR4, respectively, and the ratio of feed to gain decreased by 0.63%, 3.80%, 12.66%, and 10.76%, respectively. Serum IgA, IgG, IgM, total antioxidant capacity, and glutathione peroxidase levels increased significantly in weaned piglets in the treatment groups. Addition of 0.3% ILR significantly increased the Shannon and Simpson indices of the colonic microbiota in weaned piglets and altered the microbiota composition. Changes in metabolic profiles were observed and were primarily related to the urea cycle, amino acid metabolism, and lipid metabolism. CONCLUSION: ILR improved growth performance and serum immunological and biochemical indices and optimized the colonic microbiota structure and metabolism of weaned piglets.

Fructo-oligosaccharides promote butyrate production over citrus pectin during in vitro fermentation by colonic inoculum from pig.

OBJECTIVES: Fructo-oligosaccharide (FOS) and citrus pectin (CP) are soluble fibers with different chemical composition. However, their fermentation pattern in large intestine remains unclear. METHODS: An in vitro batch fermentation using colonic digesta from pigs as inoculum was employed to investigate the fermentation dynamics of FOS and CP. The monosaccharides and SCFAs contents were assayed by High-Performance Liquid Chromatography and Gas Chromatography, respectively. And the microbiota community was assessed by 16S rRNA gene high-throughput sequencing. RESULTS: The decline of monosaccharides in both substrates after 6 h, especially to a neglected level in FOS. FOS showed higher abundances of butyrate-producing bacteria such as Eubacterium rectale, Roseburia faecis and Coprococcus comes and butyrate compared to CP. CP stimulated the growth of pectinolytic microbe Lachnospira pectinoschiza, succinate-producing bacteria Succinivibrio dextrinosolvens, succinate-utilizing bacteria Phascolarctobacterium succinatutens and the production of acetate and propionate compared to FOS. Moreover, the relative abundances of key enzymes (e.g. butyrate kinase) involving in butyrate formation via the butyrate kinase route were upregulated in the FOS group. And the key enzymes (e.g. acetyl-CoA synthetase) associated with propionate production through the succinate pathway were upregulated in the CP group. CONCLUSIONS: FOS was preferred to ferment by butyrate-producing bacteria to yield a higher level of butyrate via the butyrate kinase pathway, while CP enhanced the cross-feeding of succinate-producing and succinate-utilizing bacteria to form propionate through the succinate pathway. These findings deepen our understanding on the fermentation characteristics of the soluble fibers, and also provide guidelines for fiber choice in precisely modulating the microbial composition and metabolism in large intestine.

Microbiota Alterations in Lung, Ileum, and Colon of Guinea Pigs with Cough Variant Asthma.

Alterations in the microbiota composition, or ecological dysbiosis, have been implicated in the development of various diseases, including allergic diseases and asthma. Examining the relationship between microbiota alterations in the host and cough variant asthma (CVA) may facilitate the discovery of novel therapeutic strategies. To elucidate the diversity and difference of microbiota across three ecological niches, we performed 16S rDNA amplicon sequencing on lung, ileum, and colon samples. We assessed the levels of interleukin-12 (IL-12) and interleukin-13 (IL-13) in guinea pig bronchoalveolar lavage fluid using the enzyme-linked immunosorbent assay (ELISA). We applied Spearman's analytical method to evaluate the correlation between microbiota and cytokines. The results demonstrated that the relative abundance, α-diversity, and ß-diversity of the microbial composition of the lung, ileum, and colon varied considerably. The ELISA results indicated a substantial increase in the level of IL-13 and a decreasing trend in the level of IL-12 in the CVA guinea pigs. The Spearman analysis identified a correlation between Mycoplasma, Faecalibaculum, and Ruminococcus and the inflammatory factors in the CVA guinea pigs. Our guinea pig model showed that core microorganisms, such as Mycoplasma in the lung, Faecalibaculum in the ileum, and Ruminococcus in the colon, may play a crucial role in the pathogenesis of CVA. The most conspicuous changes in the ecological niche were observed in the guinea pig ileum, followed by the lung, while relatively minor changes were observed in the colon. Notably, the microbial structure of the ileum niche approximated that of the colon niche. Therefore, the results of this study suggest that CVA development is closely related to the dysregulation of ileal, lung, and colon microbiota and the ensuing inflammatory changes in the lung.

The early faecal microbiota transfer alters bile acid circulation and amino acid transport of the small intestine in piglets.

The purpose of this study was to investigate the effects of faecal microbiota transfer (FMT) with lactation Min sows as faecal donor on blood immunity, small intestine amino acid transport capacity, bile acid circulation, and colon microbiota of recipient piglets. From Days 1 to 10, the recipient group (R group) was orally inoculated with a faecal suspension. The control group (Con group) was orally inoculated with sterile physiological saline. On Day 21, the results showed that the immunoglobulin A (IgA) concentration in plasma of the R group was increased (p < 0.05). The expression of 4F2hc in the jejunal mucosa and ileum mucosa of the R group was ameliorated (p < 0.05). The relative abundance of Synergistetes in the colon of the R group was increased, Proteobacteria was diminished by FMT (p < 0.05). On Day 40, the concentrations of IgA, IgG, and interleukin-2 detected in the plasma of the R group were increased (p < 0.05). FXR and fibroblast growth factor 19 gene expression was upregulated in ileum mucosa, CYP7A1 and Na+ taurocholate cotransporter polypeptide gene expression were downregulated in the liver and organic solute transporters α/ß was downregulated in colonic mucosa (p < 0.05). The relative abundance of Proteobacteria and Spirochaetes in the colon of the R group was decreased (p < 0.05). In conclusion, an early FMT with lactation Min sows as faecal donors can alter the small intestine amino acid transport capacity, bile acid circulation, and colonic microbiota of recipient piglets during lactation and after weaning.

Differential Effects of Early-Life and Postweaning Galacto-oligosaccharide Intervention on Colonic Bacterial Composition and Function in Weaning Piglets.

Recently, we proved that the early-life galacto-oligosaccharides (GOS) intervention could improve the colonic function by altering the bacterial composition in suckling piglets. However, whether the early-life GOS (ELG) intervention could have a long influence on the colonic microbiota and whether the combined ELG and postweaning GOS (PWG) intervention would have an interacting effect on maintaining colonic health in weaning piglets remain to be explored. In this study, we illustrated the differential effects of the ELG and PWG interventions on colonic microbiota and colonic function of weaning piglets. Our results showed that the ELG and PWG interventions decreased the frequency of diarrhea in weaning piglets while the PWG intervention increased colonic indexes. After 16S rRNA gene MiSeq sequencing of the gut bacteria belonging to different colonic niches (mucosa and digesta), the increase in the α-diversity of the colonic mucosal bacteria during PWG intervention was revealed. In addition, we found that both the ELG and PWG interventions enriched the relative abundances of short-chain fatty acid (SCFA) producers in different colonic niches and increased the total SCFA concentration in colonic digesta. These changes selectively modulated the mRNA expression levels of pattern recognition receptors and barrier proteins in the colonic mucosa. Of note, the combined effect of ELG and PWG effectively enhanced colonic SCFA producer enrichment and upregulated the butyrate concentration. Meanwhile, the expression levels of MyD88-NF-κB signaling and the proinflammatory cytokines were markedly reduced under the combined effect of ELG and PWG. IMPORTANCE Reducing the disorders of the gut ecosystem is an effective way to relieve weaning stresses of piglets and minimize economic losses in the modern swine industry. To this end, prebiotics have been often added to their diet during the weaning transition. In the present study, we demonstrated that the ELG and PWG interventions showed different effects on the bacterial composition of different colonic niches and on colonic function in the weaning piglets. Especially under the combined effect of ELG and PWG intervention, the expression levels of MyD88-NF-κB and the proinflammatory cytokines decreased with increasing concentrations of butyrate, which is an important microbial metabolite involved in the colon of weaning piglets. These findings further provided new insights into nutritional interventions that alleviate intestinal ecosystem dysbiosis and gut dysfunction in the piglets during the weaning transition.

Effects of the increased protein level in small intestine on the colonic microbiota, inflammation and barrier function in growing pigs.

BACKGROUND: An increased level of the dietary protein alters the colonic microbial community and metabolic profile of pigs, but it remains unclear whether this leads to colonic inflammation and impairs barrier function in growing pigs. RESULTS: Sixteen pigs (35.2 ± 0.3 kg) were infused with sterile saline (control) or soy protein hydrolysate (SPH) (70 g/day) through a duodenal fistula twice daily during a 15-day experimental period. The SPH treatment did not affect their average daily feed intake and daily weight gain (P > 0.05), but reduced colon index and length (P < 0.05). Illumina MiSeq sequencing revealed that species richness was increased following SPH intervention (P < 0.05). Furthermore, SPH reduced the abundance of butyrate- and propionate-producing bacteria-such as Lachnospiraceae NK4A136 group, Lachnospiraceae_uncultured, Coprococcus 3, Lachnospiraceae UCG-002, and Anaerovibrio-and increased the abundance of potentially pathogenic bacteria and protein-fermenting bacteria, such as Escherichia-Shigella, Dialister, Veillonella, Prevotella, Candidatus Saccharimonas, Erysipelotrichaceae UCG-006, Prevotellaceae_uncultured, and Prevotellaceae UCG-003 (P < 0.05). In addition, a lower content of total short-chain fatty acids, propionate, and butyrate and a higher concentration of cadaverine, putrescine, total biogenic amines, ammonia, and isovalerate were observed following SPH infusion (P < 0.05). Further analysis revealed that SPH increased the concentration of tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-8 in the colonic mucosa (P < 0.05). Interestingly, SPH intervention increased the expression of occludin, zonula occludens (ZO)-1, and claudin-1 in colonic mucosa (P < 0.05). Correlation analysis showed that different genera were significantly related to the production of metabolites and the concentrations of pro-inflammatory cytokines. CONCLUSION: An increased soy protein level in the small intestine altered the colonic microbial composition and metabolic profile, which resulted in the secretion of colonic proinflammatory cytokines and the increased expression of tight junction proteins.

Differential Response of Ileal and Colonic Microbiota in Rats with High-Fat Diet-Induced Atherosclerosis.

Growing evidence suggests that gut microbiota are associated with atherosclerosis (AS). However, the functional heterogeneity of each gut segment gives rise to regional differences in gut microbiota. We established a rat model of AS by feeding the rats a high-fat diet for a long period. The pathological and microbiota changes in the ileum and colon of the rats were examined, and correlations between AS and microbiota were analyzed. The aortic mesothelium of the experimental rats was damaged. The intima showed evident calcium salt deposition, indicating that the AS rat model was successfully developed. We noted varying degrees of pathological damage in the ileum and colon of the experimental rats. The 16S rDNA high-throughput sequencing showed significant differences in α-diversity, ß-diversity, and microbiota comparisons in the ileum and colon. Furthermore, the ileum and colon of AS rats showed varying degrees of intestinal microbiota disturbance. This article contributes to the study of the relationship between the microbiota in different regions of the gut and AS, and provides new approaches in gut microbiota intervention for the treatment of AS.

Fermentation of prebiotics by human colonic microbiota in vitro and short-chain fatty acids production: a critical review.

Prebiotics are known for their health benefits to man, including reducing cardiovascular disease and improving gut health. This review takes a critical assessment of the impact of dietary fibres and prebiotics on the gastrointestinal microbiota in vitro. The roles of colonic organisms, slow fermentation of prebiotics, production of high butyric and propionic acids and positive modulation of the host health were taken into cognizance. Also, the short-chain fatty acids (SCFAs) molecular signalling mechanisms associated with their prebiotic substrate structural conformations and the phenotypic responses related to the gut microbes composition were discussed. Furthermore, common dietary fibres such as resistant starch, pectin, hemicelluloses, ß-glucan and fructan in context of their prebiotic potentials for human health were also explained. Finally, the in vitro human colonic fermentation depends on prebiotic type and its physicochemical characteristics, which will then affect the rate of fermentation, selectivity of micro-organisms to multiply, and SCFAs concentrations and compositions.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

Comparison of the fermentation and bacterial community in the colon of Hu sheep fed a low-grain, non-pelleted, or pelleted high-grain diet.

Microbial fermentation in the hindgut is likely an important contributor to energy availability in ruminants, except for the rumen. This study aimed to investigate commensal bacteria in the colon influenced by diverse dietary niches. Fifteen male sheep were randomly allotted into three feeding groups: non-pelleted low-grain (CON, n = 5), non-pelleted high-grain (HG, n = 5), and pelleted high-grain (HP, n = 5) diets. The HG and HP groups had higher fermentation parameters than the CON group, especially acetate concentration (CON = 46.91; HG = 61.66; HP = 77.99). The HG diet altered the composition of commensal bacteria in the colon in comparison to the CON group, including the increase of genera related to acetate production (e.g., Acetitomaculum spp.), butyrate production (e.g., Coprococcus spp. and Subdoligranulum spp.), and starch degradation (e.g., Prevotella spp., Roseburia spp., and Oscillibacter spp.). The colon functional compendium had co-alteration with taxonomic changes that indicated non-pelleted HG diet caused a detrimental colonic niche. The HP diet specifically promoted the abundance of Ruminococcus, Olsenella, and Alloprevotella genera to achieve the highest acetate concentration and decreased the starch-degrader Roseburia spp. and Oscillibacter spp. in contrast to the HG group. Our results provide a systematic view of the microbial fermentation, community, and functional guilds in colonic digesta and mucosa in regard to using an HP diet to maintain colonic niche homeostasis under the adverse influence of the HG diet.Key Points• Non-pelleted and pelleted high-grain diets altered sheep colonic fermentation.• Non-pelleted and pelleted high-grain diets resulted in diverse microbial composition.• The pelleted method ameliorated microbial functions compared with the high-grain diet.

Prebiotics in vitro digestion by gut microbes, products' chemistry, and clinical relevance.

Several investigations have elucidated the chemistry of prebiotics based on their fermentation by the colonic microbes, which release metabolites that are often implicated in host's gut and whole body health. The present study aims at providing a preview of prebiotics and their interactions with the colonic microbiota for a slow fermentation in vitro. The metabolites produced, mainly short chain fatty acids (SCFA), their chemistry, interactions with prebiotic structural mechanisms, and beneficial impacts on the host were also reported. The present review further considers the clinical relevance of the SCFAs produced. It was deduced that the physicochemical properties of prebiotics would influence their colonic fermentation rate, microbial choice, and growth as well as SCFA type and ratios. This will in turn be of utmost clinical significance. KEY POINTS: • Prebiotics affect the composition of gut microorganisms. • The chemistry of short chain fatty acids are described. • Microbial and clinical applications of SCFAs were provided.

Early-life lactoferrin intervention modulates the colonic microbiota, colonic microbial metabolites and intestinal function in suckling piglets.

This study reports the effects of early-life lactoferrin (LF) intervention on the colonic microbiota, intestinal function and mucosal immunity in suckling piglets. A total of 60 Duroc × Landrace × Yorkshire suckling piglets from six sows were assigned to the control (CON) and LF groups in litters. The LF group piglets were fed 0.5 g/kg body weight of LF solution per day, and the CON group piglets were fed the same dose of physiological saline for a week. Six piglets from the two groups were randomly chosen and euthanised on days 8 and 21. The LF group piglets had higher ACE and Chao1 indices of colonic microbiota than the CON group piglets (P < 0.05). In addition, the LF group piglets had a higher abundance of Roseburia (P < 0.05) and a lower abundance of Escherichia-Shigella (P < 0.05) in the colonic digesta. The LF group piglets also had a higher concentration of butyrate (P < 0.05) in the colonic digesta. Moreover, the LF group piglets had a higher gene expression of occludin (P < 0.05) in the colonic mucosa. In addition, the gene expression of MUC4 was upregulated in the LF group piglets compared with that in the CON group on day 21 (P < 0.05), and the lower gene expression of TLR-4 was found in the LF group compared with the CON group on day 8 (P < 0.05). Furthermore, the concentration of IL-10 was increased in the LF group on day 8 (P < 0.05), while the LF group piglets had a higher concentration of sIgA and lower concentrations of IL-1α and IL-1ß (P < 0.05) in the colonic mucosa. These results suggest that early-life LF intervention can modulate the composition of colonic microbiota and improve the intestinal function in suckling piglets.Key Points• Early-life LF intervention significantly modulated colon microbiota.• Early-life LF intervention can improve the colon health.• The colon microbiota plays an important role in host health.

Effect of increasing levels of rice distillers' by-product on growth performance, nutrient digestibility, blood profile and colonic microbiota of weaned piglets.

OBJECTIVE: This study was conducted to evaluate the effects of diets containing different wet rice distillers' by-product (RDP) levels on growth performance, nutrient digestibility, blood profiles and gut microbiome of weaned piglets. METHODS: A total of 48 weaned castrated male crossbred pigs, initial body weight 7.54±0.97 kg, and age about 4 wks, were used in this experiment. The piglets were randomly allocated into three iso-nitrogenous diet groups that were fed either a control diet, a diet with 15% RDP, or a diet with 30% RDP for a total of 35 days. Chromium oxide was used for apparent digestibility measurements. On d 14 and d 35, half of the piglets were randomly selected for hemato-biochemical and gut microbiota evaluations. RESULTS: Increasing inclusion levels of RDP tended to linearly increase (p≤0.07) average daily gain on d 14 and d 35, and decreased (p = 0.08) feed conversion ratio on d 35. Empty stomach weight increased (p = 0.03) on d 35 while digestibility of diet components decreased. Serum globulin concentration decreased on d 14 (p = 0.003) and red blood cell count tended to decrease (p = 0.06) on d 35, parallel to increase RDP levels. Gene amplicon profiling of 16S rRNA revealed that the colonic microbiota composition of weaned pigs changed by inclusion of RDP over the period. On d 14, decreased proportions of Lachnospiraceae_ge, Ruminococcaceae_ge, Ruminococcaceae_UCG-005, and Bacteroidales_ge, and increased proportions of Prevotellaceae_ge, Prevotella_2, and Prevotella_9 were found with inclusion of RDP, whereas opposite effect was found on d 35. Additionally, the proportion of Lachnospiraceae_ge, Ruminococcaceae_ge, Ruminococcaceae_UCG-005, and Bacteroidales_ge in RDP diets decreased over periods in control diet but increased largely in diet with 30% RDP. CONCLUSION: These results indicate that RDP in a favorable way modulate gastrointestinal microbiota composition and improve piglet performance despite a negative impact on digestibility of lipids and gross energy.

Differential Effects of Breed and Nursing on Early-Life Colonic Microbiota and Immune Status as Revealed in a Cross-Fostering Piglet Model.

Nursing mother and breed can differently regulate early-life microbiota succession in pigs. However, it remains unclear whether they affect gastrointestinal microbiota and immune status, which are critical for early-life gut health. Here, an interspecific cross-fostering piglet model was employed by fostering neonatal Yorkshire and Meishan piglets to the same or another breed of sows. Jejunal and colonic microbiotas and mucosal immune parameters were analyzed at postnatal days 14 (preweaning) and 49 (postweaning). Nursing mother affected 10 genera in the colon and 3 minor genera in the jejunum. At day 14, Meishan sow-nursed piglets had lower Streptococcus suis and higher Cloacibacillus counts in the colonic digesta and larger amounts of interleukin 10 and Foxp3-positive cells in the colonic mucosa than did Yorkshire sow-nursed piglets. At day 49, nursing mother had no significant effects on cytokine expression. Breed effects were observed; Meishan piglets had lower relative abundances of Prevotella and lower gene expression of tumor necrosis factor alpha (TNF-α) than those of Yorkshire piglets at days 14 and 49. Collectively, nursing mother mainly affected preweaning colonic microbiota and immune status, while breed effects persisted after weaning. Piglets nursed by Meishan sows had different microbiota compositions and inflammatory cytokine profiles in the colon compared with those of piglets nursed by Yorkshire sows. These results highlight the different role of nursing mother and breed in affecting early gut microenvironment.IMPORTANCE Early-life gut microbiota and immune status are pivotal for postnatal growth. By using an interspecific cross-fostering piglet model, we find that change in nursing mother transiently reshapes preweaning colon microbiota and immune status, while breed shows persistent effects both pre- and postweaning. Piglets nursed by Meishan sows had lower Streptococcus suis counts and higher anti-inflammatory cytokine expression. These results highlight the significance of nursing mother in regulating early-life gut health.

Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

PURPOSE: There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. METHODS: Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. RESULTS: (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. CONCLUSIONS: The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer.

The human organism coexists with its microbiota in a symbiotic relationship. These polymicrobial communities are involved in many crucial functions, such as immunity, protection against pathogens, and metabolism of dietary compounds, thus maintaining homeostasis. The oral cavity and the colon, although distant anatomic regions, are both highly colonized by distinct microbiotas. However, studies indicate that oral bacteria are able to disseminate into the colon. This is mostly evident in conditions such as periodontitis, where specific bacteria, namely Fusobacterium nucrelatum and Porphyromonas gingivalis project a pathogenic profile. In the colon these bacteria can alter the composition of the residual microbiota, in the context of complex biofilms, resulting in intestinal dysbiosis. This orally-driven disruption promotes aberrant immune and inflammatory responses, eventually leading to colorectal cancer (CRC) tumorigenesis. Understanding the exact mechanisms of these interactions will yield future opportunities regarding prevention and treatment of CRC.

Ningxiang pig-derived Enterococcus hirae HNAU0516 ameliorates postweaning diarrhoea by promoting intestinal health and modulating the gut microbiota in piglets.

Early weaning-induced stress precipitates diarrhoea, significantly curtailing the growth performance of piglets. A pivotal contributor to this postweaning affliction is the emergence of gut bacterial dysbiosis. Enterococcus hirae, a promising probiotic, has indicated unclear effects and mechanisms on intestinal health. In this study, we investigated the effects and underlying mechanisms of oral supplementation with Ningxiang pig-derived Enterococcus hirae HNAU0516 orally supplementation on the gut bacterial community, immune response and gut barrier function in piglets. 21 d age Duroc × (Landrace × Yorkshire) piglets with a similar BW were randomly allocated to two groups. The Enterococcus hirae HNAU0516 administration group was inoculated orally with Ningxiang pig-derived Enterococcus hirae HNAU0516 throughout the trial period. Conversely, the control group received the same volume of physiological saline. Our findings revealed that Enterococcus hirae HNAU0516 supplementation effectively reduced diarrhoea rates of piglets (P = 0.010). Notably, this probiotic promoted intestinal development and enhanced intestinal barrier function. It also showed potential anti-inflammatory properties. Furthermore, Enterococcus hirae HNAU0516 supplementation significantly remodelled the colonic microbiota and increased the production of acetate (P = 0.007). In conclusion, our study highlights that Ningxiang pig-derived Enterococcus hirae HNAU0516 improves postweaning diarrhoea by promoting intestinal development, enhancing intestinal barrier function, decreasing intestinal permeability, modulating intestinal microbiota, and increasing short-chain fatty acids production.

Intrauterine Growth Restriction Affects Colonic Barrier Function via Regulating the Nrf2/Keap1 and TLR4-NF-κB/ERK Pathways and Altering Colonic Microbiome and Metabolome Homeostasis in Growing-Finishing Pigs.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different growth stages of pigs are still unclear. Therefore, this study explored through multi-omics analyses whether the IUGR damages the intestinal barrier function and alters the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs. Seventy-two piglets (36 IUGR and 36 NBW) were allocated for this trial to analyze physiological and plasma biochemical parameters, as well as oxidative damage and inflammatory response in the colon. Moreover, the colonic microbiota communities and metabolome were examined using 16s rRNA sequencing and metabolomics technologies to reveal the intestinal characteristics of IUGR pigs at different growth stages (25, 50, and 100 kg). IUGR altered the concentrations of plasma glucose, total protein, triglycerides, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels and colonic SOD-1, SOD-2, and GPX-4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased colonic IL-1ß and TNF-α levels while reducing IL-10, possibly through activating the TLR4-NF-κB/ERK pathway. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFA concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbiota community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Moreover, colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

Gut microbiota modulation, prebiotic and bioactive characteristics of date pomace polysaccharides extracted by microwave-assisted deep eutectic solvent.

This study investigated the characteristics of polysaccharides from date pomace using microwave-assisted deep eutectic solvents. The impact on the gut microbiota and probiotics growth was examined in vitro. The study also examined its antioxidant properties, ability to inhibit enzymes linked to diabetes and high blood pressure, impact on cell growth, and physical properties. The isolated MPS had an average molecular weight of 8073.38 kDa and contained mannose, galacturonic acid, galactose, glucose, and fructose in specific proportions. At a concentration of 1000 mg/L, MPS showed strong antioxidant activity, with significant scavenging rates in various tests such as DPPH (57.0 ± 1.05 %) and ABTS (66.4 ± 2.48 %). MPS displayed 77 %, 80 %, and 43 % inhibition for α-amylase, α-glucosidase, and ACE-inhibition, respectively. MPS displayed significant antiproliferative effects, achieving 100 % and 99 % inhibition against Caco-2 and MCF-7 cells at 2500 mg/L, respectively. MPS showed broad-spectrum antibacterial properties against both Gram-positive and Gram-negative foodborne bacteria. Gemmiger formicilis, Blautia species, Collinsella aerofaciens, and Bifidobacterium longum showed strong positive correlations, suggesting increased SCFA production. Network analysis indicated species correlations, with 86 % showing negative correlations with Escherichia and Enterococcus saccharolyticus. MPS was abundant in Firmicutes, Actinobacteria, and Proteobacteria phyla. Date pomace could serve as a dietary fiber source, promoting better health.

Unveiling the influence of a probiotic combination of Heyndrickxia coagulans and Lacticaseibacillus casei on healthy human gut microbiota using the TripleSHIME® system.

Probiotics are host-friendly microorganisms that can have important health benefits in the human gut microbiota as dietary supplements. Maintaining a healthy gut microbial balance relies on the intricate interplay among the intestinal microbiota, metabolic activities, and the host's immune response. This study aims to explore if a mixture of Heyndrickxia coagulans [ATB-BCS-042] and Lacticaseibacillus casei [THT-030-401] promotes in vitro this balance in representative gut microbiota from healthy individuals using the Triple-SHIME® (Simulation of the Human Intestinal Microbial Ecosystem). Metataxonomic analysis of the intestinal microbes revealed that the probiotic mix was not causing important disruptions in the biodiversity or microbial composition of the three simulated microbiota. However, some targeted populations analyzed by qPCR were found to be disrupted at the end of the probiotic treatment or after one week of washout. Populations such as Cluster IV, Cluster XVIa, and Roseburia spp., were increased indicating a potential gut health-promoting butyrogenic effect of the probiotic supplementation. In two of the systems, bifidogenic effects were observed, while in the third, the treatment caused a decrease in bifidobacteria. For the health-detrimental biomarker Escherichia-Shigella, a mild decrease in all systems was observed in the proximal colon sections, but these genera were highly increased in the distal colon sections. By the end of the washout, Bacteroides-Prevotella was found consistently boosted, which could have inflammatory consequences in the intestinal context. Although the probiotics had minimal influence on most quantified metabolites, ammonia consistently decreased after one week of daily probiotic supplementation. In reporter gene assays, aryl hydrocarbon receptor (AhR) activation was favored by the metabolic output obtained from post-treatment periods. Exposure of a human intestinal cell model to fermentation supernatant obtained after probiotic supplementation induced a trend to decrease the mRNA expression of immunomodulatory cytokines (IL-6, IL-8). Overall, with some exceptions, a positive impact of H. coagulans and L. casei probiotic mix was observed in the three parallel experiments, despite inter-individual differences. This study might serve as an in vitro pipeline for the impact assessment of probiotic combinations on the human gut microbiota.