The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis—a change in the microbial diversity—has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

Probiotic Potential of a Folate-Producing Strain Latilactobacillus sakei LZ217 and Its Modulation Effects on Human Gut Microbiota

Folate is a B-vitamin required for DNA synthesis, methylation, and cellular division, whose deficiencies are associated with various disorders and diseases. Currently, most folic acid used for fortification is synthesized chemically, causing undesirable side effects. However, using folate-producing probiotics is a viable option, which fortify folate in situ and regulate intestinal microbiota. In this study, the folate production potential of newly isolated strains from raw milk was analyzed by microbiological assay. Latilactobacillus sakei LZ217 showed the highest folate production in Folic Acid Assay Broth, 239.70 ± 0.03 ng/μL. The folate produced by LZ217 was identified as 5-methyltetrahydrofolate. LZ217 was tolerant to environmental stresses (temperature, pH, NaCl, and ethanol), and was resistant to gastrointestinal juices. Additionally, the in vitro effects of LZ217 on human gut microbiota were investigated by fecal slurry cultures. 16S rDNA gene sequencing indicated that fermented samples containing LZ217 significantly increased the abundance of phylum Firmicutes and genus Lactobacillus, Faecalibacterium, Ruminococcus 2, Butyricicoccus compared to not containing. Short-chain fatty acids (SCFAs) analysis revealed that LZ217 also increased the production of butyric acid by fermentation. Together, L. sakei LZ217 could be considered as a probiotic candidate to fortify folate and regulate intestinal microecology.

Centenarian-Sourced Lactobacillus casei Combined with Dietary Fiber Complex Ameliorates Brain and Gut Function in Aged Mice

Dietary intervention could modulate age-related neurological disorders via the gut–brain axis. The potential roles of a probiotic and the dietary fiber complex (DFC) on brain and gut function in aged mice were investigated in this study. Lactobacillus casei LTL1361 and DFC were orally administrated for 12 weeks, and the learning and memory ability, as well as the oxidative parameters, inflammatory markers, gut barrier function and microbial metabolite short-chain fatty acids (SCFAs), were investigated. LTL1361 and DFC supplementation ameliorated cognitive ability, attenuated oxidative stress in brain and inflammation in serum and colon, ameliorated gut barrier function, and increased the SCFA concentrations and gene expression of SCFA receptors. The protective effect was more significantly enhanced in aged mice treated with the combination of LTL1361 and DFC than treated with LTL1361 or DFC alone. These results could be associated with the protected morphology of pyramidal nerve cells in hippocampus of mice brain and the downregulation of apoptosis marker caspase-3 in brain and upregulation of tight junction proteins in small intestine and colon. The results indicated that Lactobacillus casei LTL1361 and DFC alleviated age-related cognitive impairment, as well as protected brain and gut function. Lactobacillus casei LTL1361 and DFC might be used as novel and promising antiaging agents in human.

High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake in young men independently of changes in thermogenesis and the gut microbiome

Diets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with insulin resistance and dyslipidemia during fructose overconsumption in humans.

Understanding the relationship between the microbiome and the structure and function of the pig gastrointestinal tract

The gut epithelium acts as a barrier to the gut environment. The integrity of the epithelial structure and function is thus critical for microbiome-host interaction. The gut microbiome can regulate the utilization and synthesis of mucin, the expressions of the intercellular junction complex, and the functioning of specific epithelial cells, such as enterochromaffin cells and stem cells in pigs. The factors involved include microbial metabolites, especially short-chain fatty acids and host-microbe co-metabolism. Recent studies have revealed the essential role of amino acid metabolism in regulating the gut microbiome and epithelial barrier. This chapter discusses how the pig gut microbiome modulates epithelial structure and function, highlighting findings that reflect the relationship between the gut microbiome, intestinal structure and function.

Sources of Dietary Fiber Affect the SCFA Production and Absorption in the Hindgut of Growing Pigs

Effects of different dietary fiber (DF) sources on short-chain fatty acids (SCFA) production and absorption in the hindgut of growing pigs were studied by an in vivo–vitro (ileal cannulated pigs and fecal inoculum-based fermentation) method. Thirty-six cannulated pigs (body weight: 48.5 ± 2.1 kg) were randomly allocated to 6 treatments containing the same DF content (16.5%), with either wheat bran (WB), corn bran (CB), sugar beet pulp (SBP), oat bran (OB), soybean hulls (SH), or rice bran (RB) as DF sources. Pigs were allowed 15 days for diet adaptation, and then, fresh ileal digesta and feces were collected to determine SCFA concentration which was normalized for food dry matter intake (DMI) and the hindgut DF fermentability. Fecal microbiota was inoculated into the freeze-dried ileal digesta samples to predict the ability of SCFA production and absorption in the hindgut by in vitro fermentation. The SH group had the largest concentration of total SCFA and propionate in ileal digesta and fecal samples of growing pigs (p < 0.05). Nonetheless, the predicted acetate, total SCFA production, absorption in the SBP group were the highest (p < 0.01), but the lowest in the OB group (p < 0.01) among all groups. Even SBP and OB group had a similar ratio of soluble DF (SDF) to insoluble DF (IDF). The CB group had high determined ileal and fecal butyrate concentration but the lowest butyrate production and absorption in the hindgut (p < 0.01). Overall, the source of DF had a great impact on the hindgut SCFA production and absorption, and SBP fiber had a great potential to increase hindgut SCFA production and absorption.

Optimised Method for Short-Chain Fatty Acid Profiling of Bovine Milk and Serum

Short-chain fatty acids (SCFA, C2-C5) in milk and serum are derived from rumen bacterial fermentation and, thus, have the potential to be used as biomarkers for the health status of dairy cows. Currently, there is no comprehensive and validated method that can be used to analyse all SCFAs in both bovine serum and milk. This paper reports an optimised protocol, combining 3-nitrophenylhydrazine (3-NPH) derivatisation and liquid chromatography-mass spectrometry (LC-MS) analysis for quantification of SCFA and β-hydroxybutyric acid (BHBA) in both bovine milk and bovine serum. This method is sensitive (limit of detection (LOD) ≤ 0.1 µmol/L of bovine milk and serum), accurate (recovery 84–115% for most analytes) and reproducible (relative standard deviation (RSD) for repeated analyses below 7% for most measurements) with a short sample preparation step. The application of this method to samples collected from a small cohort of animals allowed us to reveal a large variation in SCFA concentration between serum and milk and across different animals as well as the strong correlation of some SCFAs between milk and serum samples.

Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.

Bifidobacterium animalis subsp. lactis BB-12 Has Effect Against Obesity by Regulating Gut Microbiota in Two Phases in Human Microbiota-Associated Rats

Bifidobacterium animalis subsp. lactis BB-12 (BB-12) is an extensively studied probiotics species, which has been reported to improve the human gut microbiota. This study aimed to confirm the effects of BB-12 on high-fat diet (HFD)-induced gut microbiota disorders. The probiotic BB-12 was consumed by human microbiota-associated rats and changes in gut microbiota were compared using next generation sequencing of the fecal samples collected from the normal chow group, the HFD group, and the BB-12-supplemented group. The enterotypes switched from Prevotella dominant to Akkermansia dominant as a result of switching diet from normal chow to HFD. BB-12 conferred protection on the gut microbiota composition of the rats by increasing the abundance of Prevotella and decreasing the abundance of Clostridium, Blautia, and Bacteroides in 0–3 weeks. In addition, Prevotella-dominant enterotype was maintained, which provides improve obesity effects. A decrease in body weight and the Firmicutes/Bacteroidetes ratio were also observed at week 3. While in 4–8 weeks, the enrichment of short-chain fatty acids-producing bacteria such as Eubacterium and Parabacteroides and probiotics such as Bifidobacterium was observed. The results revealed that BB-12 against obesity by regulating gut microbiota in two phases. After a short-term intervention, BB-12 supplementation suppressed the transition from the healthy to obesity state by protecting Prevotella-dominant enterotype, whereas after a long-term intervention, BB-12 ameliorates obesity by enriching beneficial bacteria in the gut.