In this letter, assessment of the amount of fecal Faecalibacterium prausnitzii in symptomatic uncomplicated diverticular disease (SUDD) is described. Among 44 consecutive patients, comprising 15 SUDD patients, 13 patients with asymptomatic diverticulosis (AD), and 16 healthy controls (HC), the fecal amount of Faecalibacterium prausnitzii was not found to be significantly different between HC, AD and SUDD subjects (p=0.871). Moreover, its count in the HC microbiota (−4.57 ± 2.15) was lower compared with those in the AD (−4.11 ± 1.03) and SUDD subjects (−4.03 ± 1.299). This behavior seems to be different from that occurring in inflammatory bowel disease (IBD) and similar to that of other mucin-degrading species in a SUDD setting.

Chronic inflammation caused by aging, obesity, and lifestyle disturbances can lead to the production of inflammatory cytokines and insulin resistance, reducing glucose and lipid metabolism. Lactic acid bacteria (LAB) have various bioactivities, and certain types of LAB have been reported to exhibit anti-inflammatory effects. We hypothesized that LAB strains, which can strongly induce the production of anti-inflammatory cytokines by immune cells in the intestinal tract, may improve glucose and lipid metabolism by suppressing chronic inflammation. We selected Lactiplantibacillus plantarum OLL2712 (OLL2712) from the LAB library owned by Meiji Co., Ltd. based on its ability to induce the production of interleukin-10 (IL-10), optimized the culture conditions of OLL2712 for industrial applications, and verified the efficacy of the strain in animal and clinical studies. The results showed that OLL2712 bacterial cells in the exponential phase had notably higher anti-inflammatory properties than the cells in the stationary phase and led to the inhibition of chronic inflammation and improvement of glucose and lipid metabolism in animal studies. Two randomized controlled trials consisting of healthy adults with elevated blood glucose levels or body mass indices (BMIs) also showed that the intake of OLL2712 suppressed the aggravation of chronic inflammation and improved glucose and lipid metabolism. This review identified a novel LAB strain that may contribute to diabetes and obesity prevention and demonstrated its clinical efficacy. In addition, the mechanism of action of this LAB strain through the intestinal immune system was partially elucidated, and the importance of optimizing the culture conditions of LAB was clarified.

Improvements in genome analysis technology using next-generation sequencing have revealed that abnormalities in the composition of the intestinal microbiota are important in numerous diseases. Furthermore, intestinal commensal pathogens that are directly involved in the onset and exacerbation of disease have been identified. Specific control of them is strongly desired. However, antibiotics are not appropriate for the control of intestinal commensal pathogens because they may kill beneficial bacteria as well. The intestinal tract contains many viruses: most are bacteriophages (phages) that infect intestinal bacteria rather than viruses that infect human cells. Phages have very high specificity for their host bacteria. Therefore, phage therapy is considered potentially useful for controlling intestinal commensal pathogens. However, the intestinal tract is a specialized, anaerobic environment, and it is impossible to isolate phages that infect host intestinal bacteria if the bacteria cannot be cultured. Furthermore, genomic analysis methods for intestinal phages have not been well established, so until recently, a complete picture of the intestinal phage has not been clear. In this review, I summarize the importance of next-generation phage therapy based on metagenomic data and describe a novel therapy against Clostridioides difficile developed using such data.

Screening efficient strains by cell platform is cost-effective, but to date, no screening experiments have been performed for targeted lactic acid bacteria with hypoxic/reoxygenation (H/R)-treated cardiomyocytes, and their effects on the phosphoinositide 3-kinase (PI3K)/protein kinase b (Akt)/endothelial nitric oxide synthase (eNOS) pathway in myocardial infarction (MI) are unclear. Here we activated 102 strains of lactic acid bacteria and inoculated them into MRS medium for fermentation. The fermentation supernatants of the lactic acid bacteria were incubated with an H/R model of H9C2 cells. We found that Bifidobacterium longum ZL0210 had the greatest potential for inhibiting the apoptosis of H/R-induced H9C2 cells. Furthermore, it significantly increased the expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) in H9C2 cardiomyocytes, as well as the Bcl-2/Bax protein ratio, protecting damaged myocardial cells via an anti-apoptotic pathway. Intragastric administration of B. longum ZL0210 to mice for one week before and after establishment of an MI model drastically attenuated the myocardial cell hypertrophy and fibrosis of the MI mice. Meanwhile, B. longum ZL0210 significantly reduced the secretion of myocardial enzymes, increased the activity of antioxidant enzymes, and inhibited lipid-oxidative malondialdehyde (MDA) levels. Moreover, it upregulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein and the phosphorylation levels of PI3K, Akt, and eNOS, resulting in increased NO contents. In summary, we screened 102 strains of lactic acid bacteria with a cell platform and determined that B. longum ZL0210 was a favorable candidate for protecting the myocardium. We are the first to reveal the protective effects of B. longum ZL0210 for MI via activation of the PI3K/Akt/eNOS pathway through TRAIL.

It has been reported that the intake of polyamines contributes to the extension of healthy life span in animals. Fermented foods contain high concentrations of polyamines thought to be derived from fermentation bacteria. This suggests that bacteria that produce high levels of polyamines could be isolated from fermented foods and utilized as a source of polyamines for human nutrition. In this study, Staphylococcus epidermidis FB146 was isolated from miso, a Japanese fermented bean paste, and found to have a high concentration of putrescine in its culture supernatant (452 μM). We analyzed the presence of polyamines in the culture supernatants and cells of the type strains of 21 representative Staphylococcus species in addition to S. epidermidis FB146, and only S. epidermidis FB146 showed high putrescine productivity. Furthermore, whole-genome sequencing of S. epidermidis FB146 was performed, and the ornithine decarboxylase gene (odc), which is involved in putrescine synthesis, and the putrescine:ornithine antiporter gene (potE), which is thought to contribute to the release of putrescine into the culture supernatant, were present on plasmid DNA harbored by S. epidermidis FB146.

The genus Bifidobacterium comprises beneficial intestinal bacteria that play a crucial role in the regulation of human health. Traditional prebiotics are known to increase intestinal bifidobacteria by supplying a carbon source necessary for their growth. However, intestinal bifidobacteria need not only a carbon source but also a nitrogen source for growth. Moreover, the growth of bifidobacteria is known to be inhibited in a culture medium that does not contain glutamic acid. Based on these reports, we hypothesized that the combined intake of traditional prebiotics and glutamic acid would be beneficial for growth of bifidobacteria in the gut. In this study, we investigated the effects of the combination of galactooligosaccharide (GOS; traditional prebiotic material) and poly-γ-glutamic acid (γ-PGA; source of glutamic acid) and only GOS on the intestinal microbiota and health conditions (including intestinal regulation, mood status, gastrointestinal condition, skin condition, and sleep quality) in a randomized, double-blind, parallel-group comparison trial in healthy subjects. The combined intake of GOS and γ-PGA significantly increased the prevalence of B. longum compared to the intake of GOS alone. A minimum effective dose of 2.0 g GOS and 0.3 g γ-PGA improved defecation and mood status. We revealed the combined effects of GOS and γ-PGA on intestinal microbiota as well as physical condition and concluded that the delivery of glutamic acid to the large intestine with traditional prebiotics is useful as an advanced prebiotic.

Several studies have suggested that the gut microbiota affect the health of the host. For example, the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of Akkermansia muciniphila in the microbiota have been closely linked to obesity. In this study, we evaluated the effects of an anti-obesity lignan compound, arctigenin (AG), and burdock sprout extract (GSE), which contains AG, on the gut microbiota of an obese mouse model. C57BL/6J mice were fed high-fat, high-sucrose (HFHS) diets containing AG, GSE, or metformin (MF) for 8 weeks. The composition of the gut microbiota and the cecal content of short-chain fatty acids (SCFAs) were determined using 16S rRNA gene sequencing and high-performance liquid chromatography, respectively. Body weight gain was significantly suppressed in mice treated with AG, GSE, and MF. Analysis of the gut microbiota revealed that the F/B ratio was significantly reduced in the AG- and GSE-treated groups. Furthermore, the copy number of A. muciniphila in the feces was significantly increased in obese mice treated with AG and GSE. In addition, the amount of SCFAs (acetic, propionic, and butyric acids) in the cecal content and their fecal excretions were also significantly increased following AG and GSE treatment. Taken together, these results suggest that AG and GSE prevent obesity by improving the composition of the gut microbiota. Moreover, AG promoted the growth of A. muciniphila in vitro. Thus, AG and GSE may function as novel prebiotic supplements to ameliorate obesity, constipation, and intestinal disorders.

Atherosclerosis is the main cause of cardiovascular diseases, and healthy dietary habits are a feasible strategy to prevent atherosclerosis development. Camellia oil, an edible plant oil, exhibits multiple beneficial cardiovascular effects. Our previous study showed that oral administration of camellia oil attenuated hyperglycemia, fat deposits in the liver, and the atherosclerosis index in high-fat diet (HFD)-induced obese mice. Here, an atherosclerosis model of apolipoprotein E (ApoE)^−/− mice induced by HFD was used to study the effect of camellia oil on atherosclerosis, and 16S rRNA gene sequencing was used to analyze the changes in gut microbiota composition. The results showed that camellia oil significantly inhibited the formation of atherosclerotic plaques in ApoE^−/− mice, which were characterized by significantly reduced levels of serum total cholesterol and enhanced levels of serum high-density lipoprotein cholesterol. The aortic levels of interleukin-6 and tumor necrosis factor were decreased. The results of the 16S rRNA analysis showed that after camellia oil interventions, the intestinal flora of ApoE^−/− mice changed significantly, with the diversity of intestinal flora especially increasing, the relative abundances of Bacteroides, Faecalibaculum, Bilophila, and Leuconostoc increasing, and the Firmicutes/Bacteroidetes ratio and Firmicutes abundance decreasing. Collectively, our findings confirmed the promising value of camellia oil in preventing the development of atherosclerosis in ApoE^−/− mice. Mechanistically, this preventive effect of camellia oil was probably due to its lipid-lowering activity, anti-inflammatory effects, and alteration of the gut microbiota composition in the mice.

Mononuclear phagocytic cells (MPCs) are classified into monocytes (Mos)/macrophages and dendritic cells (DCs) based on their functions. Cells of MPCs lineage act as immune modulators by affecting effector cells, such as NK cells, T cells, and B cells. This study aimed to investigate the effects of Lacticaseibacillus paracasei strain Shirota (LcS) ingestion on peripheral MPCs, particularly on their expression of functional cell-surface molecules enhanced in healthy adults. Thus, twelve healthy office workers consumed a fermented milk drink containing 1.0 × 10¹¹ cfu of LcS (LcS-FM) or a control unfermented milk drink (CM) once a day for 6 weeks. Peripheral blood mononuclear cells (PBMCs) were prepared from blood samples, and immune cells and functional cell-surface molecules were analyzed. We observed remarkable differences in the expression of HLAABC, MICA, CD40, and GPR43 in plasmacytoid DCs (pDCs) between the LcS-FM and CM groups, whereas no difference was found in CD86 or HLADR expression. The LcS-FM group exhibited higher CD40 expression in both conventional DCs (cDCs) and Mos, especially in type 2 conventional DCs (cDC2s) and classical monocytes (cMos); higher percentages of cMos, intermediate monocytes (iMos), and nonclassical monocytes; and higher numbers of cMos and iMos in PBMCs than the CM group. LcS ingestion increased the expression of HLAABC, MICA, CD40, and GPR43 in pDCs and CD40 in cDCs and Mos, particularly cDC2s and cMos. These results suggest that LcS modulates the function of MPCs that may lead to the regulation of immune effector functions in healthy adults.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.

The relationships between various diseases and the human gut microbiota (GM) have been revealed. However, the relationships between the human abdominal aortic aneurysm (AAA) and GM remains unknown. The aim of this cross-sectional study was to clarify the association between the human AAA and GM. Stool samples from 30 consecutive patients with AAA before aneurysm repair and those of 30 controls without vascular diseases were analyzed by 16S rRNA gene (V3–4) sequencing using an Illumina MiSeq system and QIIME 2. There was no significant difference in age (75 vs. 75 years) or gender (80% vs. 87% males) between the groups. No significant difference in GM composition was observed in principal coordinate analysis between the two groups, whereas the AAA group showed a significantly lower abundance of Bifidobacterium adolescentis (p<0.01) at the species level than the controls. This study demonstrated that the abundance of B. adolescentis decreased in patients with AAA. This is the first study to show the characteristics of the GM in patients with AAA. Studies are needed to reveal if causal relationships exists between the human AAA and GM.

Quercetin, a flavonol present in many vegetables and fruits, has been identified as a chemoprevention agent in several cancer models. However, the molecular mechanism of quercetin’s anticancer activity is not entirely understood. MicroRNAs (miRNAs), small noncoding RNAs, have been reported to play key roles in various biological processes by regulating their target genes. We hypothesized that quercetin can exert an anticancer effect through the regulation of miRNAs. To test this hypothesis, we investigated the effects of quercetin on the expression of tumor-suppressive miRNAs in cervical cancer. Quercetin up-regulated the in vivo and in vitro expression of tumor-suppressive miRNAs miR-26b, miR-126, and miR-320a. Quercetin suppressed the level of β-catenin, encoded by catenin beta 1 (CTNNB1), by up-regulating miR-320a in HeLa cells. Moreover, quercetin increased the expression of mir-26b, mir-126, and mir-320a precursors in HeLa cells. The results from this study show that quercetin has the potential to prevent cervical cancer by regulating the expression of tumor-suppressive miRNAs.

Angiogenesis is a highly regulated biological event and requires the participation of neutrophils, which are innate immune cells, to initiate the systematic responses. Some strains of lactic acid bacteria (LAB) can be used for probiotics that provide functional modifications in our immune systems. Here, we show that oral administration of Lacticaseibacillus casei ATCC393 promoted inflammatory angiogenesis accompanied by enhanced neutrophil activity. Heat-killed L. casei (HK-LC) administration improved angiogenesis in a murine hind-limb ischemia (HLI) model. The recruitment and activity of neutrophils were enhanced by HK-LC administration under the HLI conditions. Our results provide novel evidence of an immunological contribution of LAB uptake in the prevention of or recovery from cardiovascular diseases.

The effects of lactate and probiotic lactic acid bacteria (LAB) on intestinal fermentation were analyzed using a fecal batch culture. Lactate was efficiently metabolized to butyrate and propionate by butyrate-utilizing bacteria in fecal fermentation. Probiotic LAB could stimulate butyrate and propionate production through their lactate production in fecal fermentation. It was considered that 10⁹ cfu/g or more of probiotic LAB would be required to stimulate butyrate and propionate production in the large intestine. Due to the low production of lactate, a larger number of heterofermentative LAB than homofermentative LAB would be required for this stimulation.