Structure Of Gut Microbiota Research Articles

Effects of host identity on the gut microbiota: A comparative study on three microtinae species.

Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high-throughput sequencing and bioinformatics analysis. The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species-specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high-altitude populations, were significantly higher in high-altitude N. fuscus than in low-altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than thatin L. brandtii which dwells on the earth surface. Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors.

Alterations in the Gut Microbiota Composition and Structure of Children Under 5 Years With Sepsis: A Case Report From a Federal Medical Center in Lagos State, Nigeria

Alterations in the Gut Microbiota Composition and Structure of Children Under 5 Years With Sepsis: A Case Report From a Federal Medical Center in Lagos State, Nigeria

Lactobacillus plantarum L168 improves hyperoxia-induced pulmonary inflammation and hypoalveolarization in a rat model of bronchopulmonary dysplasia

Alteration of gut microbiota can affect chronic lung diseases, such as asthma and chronic obstructive pulmonary disease, through abnormal immune and inflammatory responses. Previous studies have shown a feasible connection between gut microbiota and bronchopulmonary dysplasia (BPD) in preterm infants. However, whether BPD can be ameliorated by restoring the gut microbiota remains unclear. In preterm infants with BPD, we found variance in the diversity and structure of gut microbiota. Similarly, BPD rats showed gut dysbiosis, characterized by a deficiency of Lactobacillus, which was abundant in normal rats. We therefore explored the effect and potential mechanism of action of a probiotic strain, Lactobacillus plantarum L168, in improving BPD. The BPD rats were treated with L. plantarum L168 by gavage for 2 weeks, and the effect was evaluated by lung histopathology, lung function, and serum inflammatory markers. Subsequently, we observed reduced lung injury and improved lung development in BPD rats exposed to L. plantarum L168. Further evaluation revealed that L. plantarum L168 improved intestinal permeability in BPD rats. Serum metabolomics showed altered inflammation-associated metabolites following L. plantarum L168 intervention, notably a marked increase in anti-inflammatory metabolites. In agreement with the metabolites analysis, RNA-seq analysis of the intestine and lung showed that inflammation and immune-related genes were down-regulated. Based on the information from RNA-seq, we validated that L. plantarum L168 might improve BPD relating to down-regulation of TLR4 /NF-κB /CCL4 pathway. Together, our findings suggest the potential of L. plantarum L168 to provide probiotic-based therapeutic strategies for BPD.

Effect of Transarterial Chemotherapy on the Structure and Function of Gut Microbiota in New Zealand White Rabbits.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host's GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut-liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

Potential contributions of keystone species to intestinal ecosystem in patients with Crohn's disease.

Ravelling the central but poorly understood issue that potential contributions of keystone species to intestinal ecosystem functioning of patients with certain life-altering diseases including Crohn's disease (CD). In this study, a combination of 16S rRNA gene amplicon sequencing and amplicon-oriented metagenomic profiling was applied to gain insights into the shifts in bacterial community composition at different stages of CD course, and explore the functional roles of identified keystone species in intestinal microecosystem. Our results showed significant alterations in structure and composition of gut microbiota between CD patients and healthy control (HC) (P<0.05), but was no difference at active and remission stages. Whole-community-based comprehensive analyses were employed to identify the differential species such as Escherichia coli, Anaerostipes hadrus, and Eubacterium hallii in CD patients, with healthy populations as the control. Metagenome-wide functional analyses further revealed that the relative abundance of specialized metabolism-related genes such as cynS, frdB, serA, and gltB from these bacterial species in CD group was significantly different (P<0.05) from that in HC, and highlighted the potential roles of the keystone species in regulating the accumulation of important metabolites such as succinate, formate, ammonia, L-glutamate, and L-serine, which might have an effect on homeostasis of intestinal ecosystem. The findings identify several potential keystone species that may influence the intestinal microecosystem functioning of CD patients and provide some reference for future CD treatment.

Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer.

The gut microbiota plays a significant role in tumor pathogenesis by regulating the host metabolism and immune response, and there are few studies focused on tracking changes in the gut microbiota from the onset of lung cancer. Therefore, the aim of our study is combining preclinical and clinical research to thoroughly analyze the signatures of fecal microbiota in lung cancer, which will be useful for early diagnosis and predicting the therapeutic efficacy of lung cancer. The first part of this study analyzed the fecal metagenomic differences between patients with non-small cell lung cancer and healthy subjects, and the second part of this work constructed a murine lung cancer model to monitor changes in mouse fecal metagenomics and T cell immunology during lung cancer progression. We found that the fecal microbiota was altered in both humans and mice with lung cancer, characterized by a significantly reduced microbial diversity and number of beneficial microbes, with increases in potential pathogens. The fecal level of Akkermansia muciniphila and the gut metabolic module of the secondary bile acid metabolism were diminished in both humans and mice with lung cancer compared with healthy subjects. Splenomegaly was observed in the lung cancer mice. Flow cytometer analysis of the splenocytes revealed substantial alterations in the proportions of T cell subsets in the lung cancer mice, characterized by significant increases in CD4+Foxp3+CD25+ T regulatory cells (p < 0.05) while significant decreases in CD3+ T cells (p < 0.001), CD4+ T cells (p < 0.001), and the CD4+/CD8+ ratio (p < 0.01). Vertical and longitudinal analyses of the fecal microbiota of the two mouse groups identified some lung cancer biomarkers (including Acutalibacter timonensis, Lachnospiraceae bacterium NSJ-38 sp014337195, etc.). The fecal microbiota of the lung cancer mice had a reduced metagenomic potential for neurotransmitters (melatonin, γ-aminobutyric acid, and histamine) compared with healthy mice. In summary, this study found that the diversity, structure, and composition of gut microbiota vary between cancer and healthy conditions, ultimately leading to changes in the potential for functional metagenomics.

The Bee Gut Microbiota: Bridging Infective Agents Potential in the One Health Context.

The bee gut microbiota plays an important role in the services the bees pay to the environment, humans and animals. Alongside, gut-associated microorganisms are vehiculated between apparently remote habitats, promoting microbial heterogeneity of the visited microcosms and the transfer of the microbial genetic elements. To date, no metaproteomics studies dealing with the functional bee microbiota are available. Here, we employ a metaproteomics approach to explore a fraction of the bacterial, fungal, and unicellular parasites inhabiting the bee gut. The bacterial community portrays a dynamic composition, accounting for specimens of human and animal concern. Their functional features highlight the vehiculation of virulence and antimicrobial resistance traits. The fungal and unicellular parasite fractions include environment- and animal-related specimens, whose metabolic activities support the spatial spreading of functional features. Host proteome depicts the major bee physiological activities, supporting the metaproteomics strategy for the simultaneous study of multiple microbial specimens and their host-crosstalks. Altogether, the present study provides a better definition of the structure and function of the bee gut microbiota, highlighting its impact in a variety of strategies aimed at improving/overcoming several current hot topic issues such as antimicrobial resistance, environmental pollution and the promotion of environmental health.

Inflammatory Dietary Potential Is Associated with Vitamin Depletion and Gut Microbial Dysbiosis in Early Pregnancy.

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.

Intestinal microbial profiling and immune responses of hybrid snakehead (Channa maculata ♀ × Channa argus ♂) challenged with Nocardia seriolae strain

Nocardiosis in fish, caused by Nocardia seriolae (a kind of filamentous bacterium), is a severe disease in aquaculture, affecting over 40 species of marine and freshwater fish and causing great losses. To investigate the relationship between fish nocardiosis and the gut microbiota, we first artificially infected hybrid snakehead (female Channa maculata × male Channa argus) with N. seriolae (1.0 × 107 CFU/mL), then utilized techniques such as high-throughput sequencing of 16 S rRNA, histopathology, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to analyze the changes in microbial community structure, intestinal histopathological characteristics, and related immune genes expression in hybrid snakehead. Changes in gut microbial community structure and diversity were observed starting from day 2, followed by fluctuations on day 4, and significant alterations on day 6. Four major phyla (Actinomycetes, Proteobacteria, Firmicutes, and Bacteroidetes), particularly Actinomycetes, reflected the temporal variations in the gut microbiota structure. The composition of the gut microbiota also underwent significant changes, with beneficial microorganisms such as Lactobacillus decreasing and harmful microorganisms such as Aeromonas and Nocardia increasing. The pathological sections showed that after N. seriolae injection, the fish intestinal villi became distorted and widely spaced, with increasing damage over time, leading to severe shrinkage and atrophy by the sixth day. Additionally, immune-related genes, such as TLR2 and IRF2, exhibited higher mRNA expression levels (P < 0.01) in the intestinal tissues of the infected fish. Overall, this study provides preliminary insights into the dynamic changes in gut microbial community, immune response, and intestinal pathogenic mechanisms during N. seriolae infection in hybrid snakehead, at both the levels of gut microbial composition and mRNA expression. These findings are important for better understanding and managing Nocardia infection in fish.

Abstract 6680: High-fiber diet induces favorable gut microbiota, reduces immunosuppression, and inhibits lung cancer development

Abstract Emerging evidence suggests that resident microbial communities act as a central regulator of host homeostasis. The dynamic structure, composition, and function of gut microbiota can be influenced by numerous factors, among which nutritional profile act as most crucial determinant. Microbial consortia inhabiting the gut have been implicated in the etiology and pathogenesis of various cancers and are known to influence cancer immunosurveillance and response to immunotherapy. Despite these known associations, the underlying mechanisms by which dietary interventions such as those rich in fiber (high-fiber diet) regulate gut-immune axis in prevention of lung cancer are poorly defined. Here, we employed a human-relevant mouse model in which knockout of G-protein coupled receptor 5A (Gprc5a−/−) and exposure to tobacco lead to development of preneoplasia and lung adenocarcinoma (LUAD). Mice were randomly grouped based on dietary treatment: no fiber (control), 10% cellulose, 10% pectin-inulin following weaning (early life) or after transplant of MDA-F471 NNK-induced LUAD cells (dietary intervention). Tumor growth and volumes were most significantly reduced in mice fed a high-fiber pectin-inulin diet. Notably, anti-tumor effects of the high-fiber diet were observed in both early life and later dietary intervention settings. 16S rRNA-Seq analysis of fecal pellets revealed significant differences in gut alpha as well as beta diversity, the latter indicating clear separation of community structure between fiber-deprived versus high-fiber diet groups. Evidently, gut microbiota of pectin-inulin fed mice displayed significantly elevated relative abundance of Bacteroides sartorii, Bacteroides caecimuris, Akkermansia muciniphila and Bifidobacterium pseudolongum, taxa that have been reported to be strongly associated with favorable responses to immunotherapy. High-fiber fed mice also showed significantly reduced fractions of tumor-promoting genera such as Odoribacter and Alistipes. These effects were accompanied by widespread changes in the tumor immune microenvironment between fiber-rich and fiber-poor groups. Pectin-inulin fed mice displayed enhanced antitumor immune responses evident by remarkably increased fractions of B lineage cells, cDC1s and M1-likemacrophages and, conversely, reduced levels of activated cDC2s, M2 macrophages and polymorphonuclear myeloid-derived suppressor cells. Our findings inform on novel mechanisms by which dietary fiber robustly impacts gut consortia and immune milieu in the inhibition of LUAD. Our findings also suggest that the incorporation of dietary fiber in cancer treatment (e.g., immunotherapy) could improve outcomes for patients with LUAD. Citation Format: Manvi Sharma, Yuejiang Liu, Hannah Moreno, Inti C. Reischle, Mohamed A. Jamal, Tieling Zhou, Zahraa Rahal, Chidera O. Chukwuocha, Ke Liang, Robert R. Jenq, Matthew C. Ross, Kristi L. Hoffman, Humam Kadara. High-fiber diet induces favorable gut microbiota, reduces immunosuppression, and inhibits lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6680.

Pasteurized Akkermansia muciniphila improves immunity and relieves other toxic effects in 5-fluorouracil treated BALB/c mice

This study explored how pasteurized Akkermansia muciniphila mitigates the immunosuppressive and toxic effects of the chemotherapy drug 5-FU in mice. Pasteurized A. muciniphila raised the index of immune organs, helped restore hematopoietic functions, and greatly increased the ability of both T and B lymphocytes to multiply. This process also resulted in an increase in the percentages of CD3+ T lymphocytes as well as in the ratios of CD4+ to CD8+ T cells. Pasteurized A. muciniphila enhances serum immunoglobulin secretion. Additionally, it increased the liver's antioxidant capacity, decreased ALT and AST levels, and mitigated chemotherapy-related liver damage. Pasteurized A. muciniphila regulates intestinal mucosal immunity by influencing the gut microbiota structure. It restored small intestinal villi and crypt structures, increased intestinal sIgA levels, and increased the number of CD3+ and CD4+ T lymphocytes, thus effectively rectifying intestinal mucosal immune dysfunctions. In conclusion, pasteurized A. muciniphila significantly improved the immunosuppressive and other toxic effects induced by 5-FU in mice. These findings indicate that pasteurized A. muciniphila has the potential to be developed as a dietary strategy to reduce chemotherapy-induced toxicity.

Mulberry leaf and konjac flour compound dietary fiber improves digestion and metabolism in elderly mice with high-fish-protein diet by regulating gut microbiota structure and intestinal tissue repair

Ensuring sufficient protein intake, efficient digestion, and optimal absorption are crucial for the elderly. This study aims to investigate the potential of a compound dietary fiber, consisting of mulberry leaf and konjac flour (CMK), to enhance the digestion and absorption of a high-fish-protein diet in elderly mice. Results showed that CMK effectively reduced the number of unique peptide segments, generated short-chain fatty acids (SCFA) in feces, improved the content of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), amino acid, and urea nitrogen in serum, activated the contents of pepsin, trypsin, and erepsin, and enhanced the expression of glutamate dehydrogenase (GDH), peptide transporter 1 (PepT1), and aminopeptidase N (APN). Furthermore, CMK demonstrated its ability to decrease the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP), while increase the abundance of beneficial bacteria, such as Lactobacillus and Blautia. In conclusion, CMK proved effective in enhancing the digestion and metabolism of protein in elderly mice through the regulation of gut microbiota structure and intestinal tissue repair.

Pueraria lobata Resistant Starch Regulating Lipid Metabolism and Gut Microbiota in High‐Fat Diet Mice

AbstractPueraria lobata resistant starch (PLRS) is prepared by modifying Pueraria lobata starch with pullulanase, and the PLRS modulate lipid metabolism disorders and gut microbiota structure are hypothesized in high‐fat diet (HFD) mice. The results reveal that the PLRS can alleviate lipid metabolism disorders by significantly upregulating the abundance of Akkermansia, Lactobacillus, Blautia, and Dubosiella, but markedly downregulating Staphylococcus in HFD mice. The PLRS may decrease the gain of weight, biochemical index, ameliorate hepatic impairment, and histopathological. Molecular mechanisms have elucidated that the PLRS may exert reducing fat accumulation and stabilize the gut microbiota effects through the modulation of the fatty acid metabolic signaling pathway and the PPAR signaling pathway. Therefore, these results suggest that this prebiotic carbohydrate may regulate lipid metabolism and gut microbiota in HFD mice and can be used to prepare healthy lipid‐lowering functional foods to attenuate obesity problems.

Analysis of the Difference of Intestinal Microbes in Muchuan Black-bone Chickens with Two Skin Colors

Background: Skin color is an important economic trait in black-bone chicken production and it has been identified that the gut microbiota is an important factor in animal health and physiology. However, it is unknown about whether the gut microbiota in black-bone chickens is connected to the coloration of chicken skin. Methods: To investigate the relationship between the gut microbiota and skin coloration, comparing the differentiation of the gut microbiota structure and abundances in black- (B group) and white-skinned (W group) Muchuan black-bone chicken. Here, we characterized the microbiota in the jejunal contents of both the B and W groups using the Illumina MiSeq platform, targeting the genomic V4 region of the 16S rRNA gene. Result: In terms of community richness, the ACE community richness index of the B group was significantly higher than that of the W group (p less than 0.05) and the proportion of unique OTUs was higher in group B than in group W. According to the species annotation and abundance information of all samples at the genus level, Parabacteroides, Faecalicoccus and Alistipes were enriched in group B, whereas Actinomyces, Elstera and Nosocomiicoccus were enriched in group W. In the evolutionary branch diagram, the relative abundances of Enterobacteriaceae (Gammaproteobacteria, Enterobacteriales) were significantly higher in group B than in group W (LDA Score greater than 4). Our data provide a basis for the hypothesis that the discriminating bacterial taxa in gut is associated with the feature variants for skin coloration of Muchuan black-bone chickens, which were fed in the same feed and stocking niches.

Nodakenin Ameliorates Ovariectomy-Induced Bone Loss by Regulating Gut Microbiota.

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using μCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.

Gracilaria extract reduce hyperglycemia by modulating gut microbial and short chain fatty acids

High blood sugar is the main feature of diabetes. In order to effectively regulate blood glucose levels, in this study, we used Gracilaria as raw material and found that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) were beneficial for decreasing fasting blood glucose, improving insulin resistance, enhancing the function of islet β-cells, and regulating the abnormal increase of TC, TG, LDL-c caused by hyperglycemia in diabetic mice. Moreover, 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) affected the gut microbiota structure of diabetic mice, decreased the Firmicutes/Bacteroidetes ratio, increased the abundance of Lactobacillus and Collinsella etc. and reduced the abundance of Helicobacter and Oscillibacter etc. In addition, the content of acetic acid and butyric acid in metabolites of short-chain fatty acids had increased, which had the effect of regulating blood glucose level. The results have showed that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) are potential marine foods for maintaining blood sugar health.

The effect of in vitro simulated colonic pH gradients on microbial activity and metabolite production using common prebiotics as substrates

BackgroundThe interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon.ResultsHere we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates.ConclusionsTogether, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research.

Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice.

The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.

(−)-Epicatechin ameliorates type 2 diabetes mellitus by reshaping the gut microbiota and Gut–Liver axis in GK rats

As one of the most abundant plant polyphenols in the human diet, (−)-epicatechin (EC) can improve insulin sensitivity and regulate glucose homeostasis. However, the primary mechanisms involved in EC anti-T2DM benefits remain unclear. The present study explored the effects of EC on the gut microbiota and liver transcriptome in type 2 diabetes mellitus (T2DM) Goto–Kakizaki rats for the first time. The findings showed that EC protected glucose homeostasis, alleviated systemic oxidative stress, relieved liver damage, and increased serum insulin. Further investigation showed that EC reshaped gut microbiota structure, including inhibiting the proliferation of lipopolysaccharide (LPS)-producing bacteria and reducing serum LPS. In addition, transcriptome analysis revealed that the insulin signaling pathway may be the core pathway of the EC anti-T2DM effect. Therefore, EC may modulate the gut microbiota and liver insulin signaling pathways by the gut–liver axis to alleviate T2DM. As a diet supplement, EC has promising potential in T2DM prevention and treatment.