Bioscience of Microbiota Food and Health

Ingestion of dark chocolate improves constipation and alters the intestinal microbiota in Japanese women
Ito H, Shimonaka A, Natsume M, Yonekura K, Fukasawa T, Ito S, Sawazaki A, Tamura K, Kimura I and Koga J
In a previous study, we found that proteins from cacao beans (cacao proteins) were resistant to digestive enzymes and that ingestion of the indigestible cacao proteins promoted defecation and altered the intestinal microbiota in mice. Therefore, we investigated whether ingestion of dark chocolate containing high amounts of cacao proteins improves constipation and alters the intestinal microbiota in Japanese women. Bowel movement frequency and stool amount after dark chocolate ingestion were significantly higher than before dark chocolate ingestion and significantly higher than after ingestion of white chocolate with no cacao proteins. Next, stool samples were collected, and the intestinal microbiota was analyzed by next-generation sequencing-based 16S rRNA. There was no significant difference in the α-diversity index of the gut microbiota between before and after ingestion of white chocolate, but the α-diversity index of the gut microbiota after ingestion of dark chocolate was significantly higher than before ingestion. The relative abundances of and in the fecal microbiota after dark chocolate ingestion were significantly higher than before dark chocolate ingestion and significantly higher than after white chocolate ingestion. The relative abundances of , , and in the fecal microbiota after dark chocolate ingestion were significantly higher than before ingestion. Spearman correlation analysis revealed a correlation between the stool amount and relative abundances of and in the dark chocolate ingestion group. These results indicate that ingestion of dark chocolate improved constipation in humans and promoted increase of the relative abundances of butyrate producing bacteria such as , , , , and in the intestinal microbiota.
Correlation between differences in the intestinal flora structure and Chinese medicine evidence in patients with Wilson disease-related liver fibrosis analyzed via high-throughput sequencing technology
Pu Y, Zhang X, Zhang J, Xie D, Wang H, Chen H, Ma Y, Peng N, Li R and Ye H
To observe the composition and abundance of the intestinal flora in patients with Wilson disease (WD)-related liver fibrosis and analyze the correlation between the composition of intestinal flora of patients and the evolution of evidence from Chinese medicine, we selected 237 patients with WD-related liver fibrosis and 30 healthy volunteers from the Brain Disease Center of Anhui Provincial Hospital of Chinese Medicine. The patients with WD-related liver fibrosis were divided into 5 groups according to traditional Chinese medicine (TCM) evidence (dampness-heat syndrome, group A; intermingled phlegm and blood stasis syndrome, group B; liver wind stirring up internally syndrome, group C; yin deficiency of the liver and kidney syndrome, group D; and yang deficiency of the spleen and kidney syndrome, group E) and a group healthy volunteers (group F), which served as the control. Stool samples were obtained from the patients in the 6 groups. The 16S rRNA sequencing technique was used to analyze the intestinal flora of the different TCM evidence groups of WD patients and the healthy control group and subjected to a statistical analysis. The intestinal flora abundance was significantly lower in patients with WD-related liver fibrosis than in healthy controls, and the decrease in strain content was more significant in patients with deficiency evidence in groups D and E. In terms of the structure of the phylum-level flora, the Firmicutes phylum was still the dominant phylum, but the contents of the evidence-type groups all decreased, with the most obvious decreases in groups D and E. The results for the Actinobacteria phylum were similar, whereas the opposite was true for the Proteobacteria phylum. The section-level and genus-level results corresponded to the gate level. The intestinal flora of the WD-related liver fibrosis patients and healthy controls differed in terms of abundance and intestinal flora structure, and there were also differences between different Chinese medicine certificates.
Optimization of growth conditions and the inducer concentration for increasing spike protein expression in recombinant and its kinetic modeling
Mubarak TH, Maulita S, Adianingsih OR, Tebbens JD, Shimosato T and Yurina V
bacterium can be genetically modified to transport the spike protein from SARS-CoV-2, making it a potential candidate for a COVID-19 mucosal vaccine. This study aimed to optimize the nisin concentration, pH, incubation time, and media composition to induce spike protein expression. The concentrations of nisin used in this study ranged from 0 to 40 ng/mL, the incubation period was 3 to 24 hr, and the pH of the growth media ranged from 4 to 8. The media was also supplemented with various yeast extract and sucrose concentrations. The highest protein band intensity was observed at a concentration of 40 ng/mL and an incubation period of 9 hr. Supplementation with 4% w/v yeast extract and 6% w/v sucrose significantly increased the expression of HCR spike protein. simulation suggested a maximal protein band intensity of 70.95 arbitrary units, while the nisin concentration needed to produce half the maximal protein band intensity was estimated to be 9.599 ng/mL. No significant difference in spike protein expression was found between pH variations. The media composition, inducer, and incubation time strongly affect the spike protein expression.
strain Shirota suppresses upper respiratory tract infections and activates mononuclear phagocytic cells in healthy Japanese office workers: a randomized, double-blind, controlled trial
Naito T, Morikawa M, Maki A, Kato-Nagaoka N, Hagihira Y, Iwata A, Watanabe O, Shida K, Matsumoto S and Hori T
Certain probiotics prevent upper respiratory tract infections (URTIs) by activating immune cells, particularly mononuclear phagocytic cells (MPCs). However, the influence of strain Shirota (LcS), a representative probiotic strain, remains underexplored. This study aimed to investigate the effects of LcS ingestion on URTIs and MPC activation. Two hundred healthy workers aged 23-59 consumed a fermented milk drink containing 4.0 × 10 CFU of LcS (LcS-FM) or a control unfermented milk drink (CM) daily for 28 days during winter. The incidence and severity of URTIs were surveyed using a questionnaire. Peripheral blood mononuclear cells (PBMCs) and serum samples were analyzed for immune cell subsets, cell surface molecules, and cytokines. The LcS-FM group showed a significantly lower incidence and severity of URTIs than the CM group. Notably, the incidence, cumulative incidence, and severity of URTI symptoms were markedly suppressed after 14 days of consumption. LcS-FM also affected MPC activation during this period. The expression of HLA-DR on conventional dendritic cells (cDCs) and monocytes (Mos) was significantly higher in the LcS-FM group on days 14 and 28, along with the expression of CD86 on cDCs on day 14. Among the study participants positive for serum interferon (IFN), the IFNα2 concentration in the LcS-FM group was higher than that in the CM group on day 28. These findings suggest that LcS suppresses the incidence and severity of URTIs in healthy adults, which is associated with the activation of cDCs and Mos.
The effect of culturing temperature on the growth of the most dominant bacterial species of human gut microbiota and harmful bacterial species
Shimokawa H, Sakakibara H, Ami Y, Hirano R and Kurihara S
In recent years, the gut microbiota has attracted attention due to reported associations with various diseases and health conditions. Gut bacteria have been constantly cultured at 37°C, potentially limiting the understanding of the interaction between them and the host. However, the most dominant human gut microbial species have not been extensively cultured at temperatures other than 37°C. In this study, we analyzed the effects of various culturing temperatures on the growth of the 51 most dominant commensal species as well as 3 harmful bacteria, including , a food poisoning bacterium, in the human intestine. The results showed that the growth of predominant gut microbes varied minimally at body temperatures conducive to human survival but that the growth of several bacteria involved in butyrate production in the intestinal lumen was repressed at temperatures other than 37°C. When cultured at 50°C, the growth of was less inhibited than that of other bacterial species. In addition, the growth of some gut bacteria was unaffected by a body temperature range that was not suitable for human survival.
Gandouling improves Wilson's disease liver fibrosis by modulating intestinal flora: a randomized, double-blind, placebo-controlled trial
Pu Y, Li R, Chen H, Ma Y, Ye H, Zhang X and Zhang J
Based on liver FibroTouch technology combined with 16S rRNA gene sequencing technology, this study aimed to explore the changes of liver fibrosis indexes and intestinal flora in Wilson's disease (WD) improved by Gandouling (GDL). Ninety patients with WD hepatic fibrosis at the Brain Disease Center of the Anhui Provincial Hospital of Traditional Chinese Medicine were included and randomly divided into an observation group and a control group for a 48-day randomized, double-blind, placebo-controlled trial. Patients in both groups were treated with conventional sodium dimercaptopropanesulfonate, to which GDL was added in the observation group, while the control group was given the corresponding placebo treatment. Before and after treatment, liver stiffness was assessed, blood samples were collected for laboratory tests, and stool samples were collected for 16S rRNA sequencing. Supplementation with GDL significantly improved liver stiffness and non-invasive liver fibrosis modeling indicators, while alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, bile acid, platelets, hyaluronic acid and laminin levels were also significantly improved (p<0.05). Other parameters showed no significant changes. The results of intestinal microbial testing showed that the microbial diversity and composition of the patients in the observation group underwent significant optimization, in which the number of probiotics rose but the number of pathogenic and opportunistic pathogens declined and even basically returned to the normal range. GDL combined with conventional liver-protecting and copper-removing treatments can effectively improve patients' liver fibrosis-related indexes. Furthermore, GDL has the ability to regulate the composition and diversity of the intestinal flora and promote reconstruction of the intestinal microbial community, which in turn may reverse the state of hepatic fibrosis.
Antibiotic combination therapy for the induction and maintenance of remission in patients with ulcerative colitis
Nishikawa Y, Ohkusa T, Shibuya T, Osada T, Uchiyama K and Sato N
Dysbiosis of the gut microbiota has recently been identified as a therapeutic target for ulcerative colitis. We reported the effectiveness of antibiotic combination therapy (ATM therapy) for the induction and maintenance of ulcerative colitis remission. In this study, we aimed to investigate the long-term effectiveness of ATM therapy in a larger cohort. A prospective open-label trial was undertaken with 311 adult ulcerative colitis patients. The combination of oral amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. was administered to patients daily for 2-4 weeks in addition to their conventional medication. Clinical assessments were performed using the partial Mayo score at baseline; at treatment completion; and at 3, 6, 9 and 12 months. Endoscopic evaluations were performed using the Mayo endoscopic score at baseline, 3 months, and 12 months. The compliance rate was 95.7%. The response and remission rates were 75.2% and 30.9% at completion, 62.7% and 29.6% at 3 months, 48.2% and 27.7% at 6 months, 37.9% and 24.4% at 9 months, and 35.4% and 24.4% at 12 months. The most frequent adverse events were diarrhea and fever. No life-threatening adverse events were observed during the trial. ATM therapy effectively led to long-term clinical response and remission in patients with active ulcerative colitis symptoms. However, further investigations are needed for the standardization of antibiotic therapy for ulcerative colitis in the future.
Modulation of the gut microbiota by dietary intervention with improves the health status of Wistar rats with metabolic syndrome
Morales-Cano KL, Rivera-Alamillo YC, Oliart-Ros RM and Peña-Montes C
The gastrointestinal tract is an ecosystem with heterogeneous patterns, distributions, and environments, resulting in different microbial compositions in each gut segment. The relationship between diet and microbiota determines this heterogeneity. Consumption of diets high in fat and carbohydrates (HLHC) is associated with gut dysbiosis, low microbial diversity, and metabolic syndrome (MetS). Functional fiber consumption improves the profile and diversity of the gut microbiota (GM); it stimulates the production of short-chain fatty acids (SCFAs), which act as signaling molecules that maintain the gut barrier integrity and induce hormone synthesis that regulates satiety and glucose metabolism, reducing some MetS parameters. The effect of a dietary intervention with (At), a cactus rich in fiber, antioxidants, amino acids, and minerals traditionally consumed by the Mexican population, is reported here. For this purpose, Wistar rats were randomly divided into three study groups: a control (C) group, a MetS group, and an At-supplemented group. In the MetS and At groups, an HLHC was administered for 12 weeks, inducing MetS. After 18 weeks, stool samples were collected for microbiota sequencing. HLHC administration favored Firmicutes and decreased the abundance of Bacteriodetes at the phylum level in the MetS group. At the genus level, the dietary intervention with At increased the presence of , , , , and , reflecting the effect of consumption on GM. At diet administration reduced body weight; the plasma glucose, insulin, and lipid levels; and insulin resistance.
Ingestion of egg white after acquisition of oral tolerance with heated egg white in OVA-sensitized mice caused severe allergic symptoms
Watanabe H, Toda M, Hachimura S and Nakajima-Adachi H
Heated eggs have often been used for oral immunotherapy of egg allergy because of their lower allergenicity than raw eggs. Furthermore, recent guidelines recommend the earlier introduction of well-cooked eggs to the diet as a supplementary food and protective measure against food allergy in infants. However, the influence of cooking with heat on the allergenicity and tolerogenicity of egg white (EW) antigen in individuals with egg allergy is not well understood. We investigated this by feeding ovalbumin (OVA)-sensitized inbred mice EW heated at 80°C for 15 min (80EW), 100°C for 5 min (100EW), or 121°C for 40 min (121EW). Only 100EW resolved enteritis, and it produced more effective tolerogenicity to OVA than EW. The state of enteritis and tolerogenicity for 80EW was almost the same as that for EW. Th1 responses to short-term feeding were observed with 121EW. We then investigated allergy recurrence after continuous feeding with the 100EW diet. Of note, however, the oral tolerance acquired with 100EW or EW was not effective against allergic recurrence in response to EW, because of residual high levels of serum OVA-specific IgE and residual infiltrated mast cells in the intestine. Furthermore, the recurrence of allergic symptoms in response to EW was more severe when oral tolerance was acquired with 100EW rather than with EW. Our results suggest that patients must be careful not to inadvertently consume EW, even if clinical tolerance to heat-treated EW has been achieved.
Beneficial effects of probiotic supplementation ( Dad-13) on body weight, liver function, and liver histopathological features in non-alcoholic fatty liver disease (NAFLD) model Sprague-Dawley rats
Minhajat R, Afifah H, Cangara H, Muis M, Bukhari A and Wahyuni S
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by hepatic fat accumulation unrelated to alcohol consumption, with its prevalence rising alongside obesity rates. The gut-liver axis reveals that gut microbiota and metabolites significantly impact NAFLD development and progression. This study aimed to investigate the effects of probiotic Dad-13 on body weight, liver function, and histopathological features in a rat model of NAFLD. The experimental protocol involved administering probiotic Dad-13 at a dose of 3 × 10 CFU/g over six weeks to rats with NAFLD induced by a high-fat and high-fructose (HFFr) diet. The results demonstrated significant reductions in body and liver weight, improved liver function (serum lipopolysaccharide binding protein, aspartate aminotransferase, and alanine aminotransferase levels), and improved the non-alcoholic liver activity score in rats fed HFFr diets supplemented with probiotics. These findings suggest that supplementation with probiotic Dad-13 is a promising therapeutic intervention for NAFLD.
Probiotic-derived extracellular vesicles: a novel weapon against viral infections
Shi Y, Li S and Yang S
Viral diseases remain a significant global challenge. Although vaccination is the primary strategy for preventing viral infections, the rapid evolution of viruses and their divergence from existing vaccines limit vaccine efficacy. Therefore, novel and safe alternatives to combat viral infections are urgently needed. Probiotic-derived extracellular vesicles (PEVs), lipid bilayer-enclosed nanoparticles, exhibit potential as safe alternatives to live bacteria for treating viral diseases. These vesicles deliver antiviral molecules through mechanisms such as blocking viral adsorption/invasion and modulating host immune responses. This review systematically summarizes the biological characteristics of PEVs, their antiviral mechanisms, and their potential applications against respiratory, enteric, and enveloped viruses. Additionally, recent advances in engineering strategies, clinical translation challenges, and future directions for PEVs are discussed.
Extracellular vesicles shed by macrophages co-cultured with No. 14 reduce adipocyte size in mice fed a high-fat diet
Tsuruta T, Ito Y and Sonoyama K
Our previous study showed that the intragastric administration of No. 14 reduces adipocyte size in white adipose tissue of high-fat diet (HFD)-induced obese mice. We also suggested that the anti-inflammatory effect of No. 14 in white adipose tissues is mediated, at least in part, by circulating exosomes, a type of extracellular vesicle (EV). Therefore, the present study examined whether EVs mediate the adipocyte size-reducing effect of No. 14. Macrophages derived from mouse bone marrow were co-cultured with No. 14, and EVs were isolated from the culture supernatant by ultracentrifugation. C57BL/6J mice fed an HFD were intravenously administered the EVs 5 times a week for 7 weeks. We found that the average adipocyte size was significantly lower in mice administered EVs isolated from the culture supernatant of macrophages co-cultured with No. 14 than in those administered EVs isolated from the culture supernatant of macrophages without co-culture and those administered PBS. In adipocytically differeintiating 3T3-L1 cells, supplementation of EVs isolated from the culture supernatant of macrophages co-cultured with No. 14 reduced adipogenesis, as evidenced by AdipoRed staining. Furthermore, the mRNA levels of adipogenesis-related genes and insulin-induced glucose uptake were also reduced by supplementation with EVs isolated from the culture supernatant of macrophages co-cultured with No. 14. These results suggest that circulating EVs shed by macrophages are involved in the adipocyte size-reducing effect of No. 14 by reducing adipogenesis-related gene expression and glucose uptake in adipocytes.
Genetic analysis of a β-1,3/1,4-glucan utilization gene cluster in JCM 13464
Oyama M, Hashimoto Y, Sagara Y, Kitamura N, Kishino S, Obinata H, Tomita H and Sugiyama Y
Barley β-glucan (BGL), a dietary fiber composed of β1,3- and β1,4-linked glucose units, confers various health benefits, including anti-diabetic effects. A previous study reported that the anti-diabetic effect of BGL was associated with gut bacteria, particularly . Recently, a study using recombinant proteins revealed the biochemical characteristics of proteins encoded by the polysaccharide utilization locus 4 (PUL4), which is implicated in BGL assimilation. However, the precise physiological roles of PUL4 remain unclear. In this study, we used gene disruption in JCM 13464 (=DSM 18205; also known as CB7) to investigate the physiological functions of PUL4 under BGL-supplemented conditions. Deletion of significantly reduced bacterial growth, as well as acetic and succinic acid production, indicating that PUL4 is essential for efficient BGL assimilation and key metabolite generation. Moreover, although PUL4 contributed to BGL and lichenan utilization, cello-oligosaccharide assimilation did not require PUL4, indicating the presence of additional metabolic systems in JCM 13464. Strain comparisons showed that one of the four strains assimilated BGL despite lacking PUL4, implying that some strains may possess alternative BGL-degrading loci other than PUL4. These findings provide direct evidence that PUL4 is an indispensable gene cluster for BGL assimilation by JCM 13464. Because PUL4 enhances the biomass yield on BGL, it likewise boosts total acetate and succinate formation, potentially generating health benefits.
Continuous intake of galacto-oligosaccharides containing syrup contributes to maintaining the health of household cats by modulating their gut microbiota
Hokkyo A, Kakiyama S, Shiwa Y, Kaga C, Kobayashi T, Nomoto K and Harima-Mizusawa N
The study of the relationships between the microbiota and intestinal environment of companion animals has gained increasing attention, particularly concerning health and disease. Previously, we demonstrated that continuous intake of galacto-oligosaccharides (GOS), a prebiotic, can improve the health of household dogs by modulating their gut microbiota. Given the potential health benefits of GOS in cats, we conducted a single-arm open-label study to evaluate the effects of a GOS-containing syrup on the gut microbiota and its metabolites in healthy cats. The study included 25 household cats and was conducted over 12 weeks. Each cat was fed 1.2 g of a GOS-containing syrup per day, equivalent to 0.5 g of GOS. Before the start of the study (week 0), during the 8-week intake period (weeks 4 and 8), and 4 weeks after the intake period (week 12), fecal microbiota, fecal organic acid and putrefactive product concentrations, fecal odor, and serum uremic toxin concentrations were assessed. The results showed that the levels of acetic acid-producing significantly increased as a result of GOS intake. Additionally, and levels significantly decreased and increased, respectively, due to GOS intake. Furthermore, the concentrations of acetic, propionic, and butyric acids in feces significantly increased, whereas serum phenyl sulfate levels decreased significantly. These findings suggested that continuous GOS intake may contribute to the health of household cats.
Gut microbiome in adult Asians with obesity, type 2 diabetes mellitus, and a combination of obesity and type 2 diabetes mellitus
Widjaja N, Agustina C, Felicia F, Wijaya F, Limanjaya J, Yulandi A, Waturangi DE, Simatupang ST, Tan S and Tjandrawinata RR
Obesity and type 2 diabetes (T2D) are two of the most common health problems in the world, particularly in adult Asians, with a significant impact on morbidity and mortality. Numerous studies have revealed that the gut microbiome of people with obesity and T2D differs significantly from those of healthy people. Those who suffer from certain illnesses often encounter disruption in their gut microbiome, leading to a decrease in richness diversity and diminished microbial activity. This disruption can also result in the loss of the gut mucosal barrier, increased gut permeability, and most likely, the development of a leaky gut. Recent studies have also emphasized the essential role of the gut microbiome in these conditions. However, conflicting findings were found between one study and another investigation. Therefore, this paper aims to provide an overview of gut microbiome characteristics in adult Asians with obesity, T2D, and the combination of both. In addition, this paper elaborates on the current understanding regarding the association of the gut microbiome with health status, thereby serving as a foundation for developing probiotics or prebiotics to modulate the gut microbiome and improve metabolic health.
Administration of a probiotic supplement attenuates nonalcoholic fatty liver disease by reducing hepatic lipid accumulation, oxidative stress, and inflammation
Chonpathompikunlert P, Yingthongchai P, Tateing S, Amatachaya A, Kaewbutra S, Chaiyawan N, Lekchaoum T, Chaipanya C, Malakul W and Khongrum J
Due to the requirement for a novel and effective treatment for non-alcoholic fatty liver disease (NAFLD), this study aimed to determine the effects of a novel supplement containing and on oxidative stress, inflammation, glucose and lipid metabolism, lipid accumulation, and liver function in the fructose-induced NAFLD rat model. To investigate the involvement of molecular pathways and validate a preclinical study, NAFLD was induced by feeding them fructose-containing drinking water (20% w/v) for 12 consecutive weeks. The fructose-induced male rats were administered a mixture of TISTR 2529 and TISTR 2736 at a dose of 2 × 10 CFU/mL during weeks 0 to 12, daily. Weight and food intake were recorded daily. The production of oxidative stress, expression of the TNF-α, SREBP-1c, liver enzymes, and lipid profiles, including the densities of lipid droplets in liver cells, were also evaluated. The results revealed that fructose-induced rats co-treated with the mixed probiotics had significantly decreased body weights, triglycerides, cholesterol, and liver enzymes. Furthermore, the expression of TNF-α, MDA, and SREBP-1c and the densities of lipid droplets in the liver tissue were reduced. Based on the results, the novel probiotic supplement containing TISTR 2529 and TISTR 2736 might alleviate NAFLD by normalizing oxidative stress, inflammation, lipid metabolism, and lipid accumulation in the liver of NAFLD-induced model rats.
Effect of long-term consumption of strain Shirota-fermented milk on weight loss in the institutionalized oldest old: an exploratory study
Naito E, Kato-Kataoka A, Hayashi N, Kurakawa T, Naito T, Moriyama-Ohara K, Kano M, Matsumoto S, Tsuji H and Fukuda R
Older individuals with care needs and lower body mass indices (BMIs) are more likely to be malnourished. Unintentional weight loss, an indicator of malnutrition, significantly impacts the physical function and poor prognosis of older adults. This study aimed to explore the effects of long-term consumption of strain Shirota-fermented milk (LcFM) on body weight in the oldest old among nursing-home residents. In total, 118 participants in 21 nursing homes were recruited. Owing to its preliminary nature, randomization and blinding were not conducted, and subjects in the intervention (consuming LcFM daily for 12 months) and non-intervention groups were recruited separately from different nursing homes. Changes in body weight and the proportion of participants with ≥5% body-weight loss were assessed at 6 and 12 months. As intergroup discrepancies in care-needs levels were observed at baseline, a subgroup analysis by these levels was conducted to align baseline characteristics. In the mild care-needs level subgroup (long-term care level ≤2), the LcFM group had a significantly lower proportion of participants with ≥5% weight loss than the control group. Additionally, a subgroup analysis by BMI demonstrated that an effect of LcFM on body weight decline was observed only in the subgroup with a BMI <22 kg/m, which indicates malnutrition risk in older adults. In conclusion, long-term consumption of LcFM might reduce unintentional weight loss in the institutionalized oldest-old individuals who have a risk of malnutrition and have a mild care-needs level. To confirm these preliminary results, further well-designed randomized trials will be required (UMIN000036684).
The effects of functional biscuits on intestinal mucosal microbiota composition, brain function, and antioxidant activity
Shen J, Fang L, Tan Z, Xiao N and Peng M
Protecting brain health is one of the current focal points of public concern. Medicinal foods that promote brain health, such as Bl, black sesame seeds ( L.), walnuts ( L.), jujube ( Mill.), , and seeds, possess antioxidant and neuroprotective properties, as well as modulating effects on the intestinal microbiota. This study evaluated the effects of functional biscuits formulated with these medicinal foods on the intestinal mucosal microbiota, brain function, and antioxidant activity in mice. Forty male SPF-grade C57BL/6J mice were randomly divided into a blank control group (NG), low-dose functional biscuit group (GLG), medium-dose functional biscuit group (GMG), and high-dose functional biscuit group (GHG). After 42 days of continuous feeding with the functional biscuits, changes in the richness, diversity, and community structure of the intestinal mucosal microbiota were observed. Compared with the NG group, norepinephrine (NE) levels in the hippocampus significantly increased in the GLG, GMG, and GHG groups, while gamma-aminobutyric acid (GABA) levels showed no significant difference. In the GMG and GHG groups, malondialdehyde (MDA) levels in the liver significantly decreased, and acetylcholine transferase (ChAT) levels in the hippocampus significantly increased. Additionally, multiple bacterial genera were found to be correlated with the NE, ChAT, and MDA levels. These findings indicate that functional biscuits have effects on modulating the intestinal mucosal microbiota composition, enhancing brain function, and exhibiting antioxidant activity, making them a beneficial functional food for brain health.
Efficacy of sclareol based on 16S rDNA sequencing in modulating gut microbiota composition in estradiol-treated mice
Huang YJ, Wong J, Chiang YF, Huang KC, Chen HY, Cheng TS, Ali M, Shieh TM and Hsia SM
Dysmenorrhea, the most prevalent gynecologic complaint among adolescent females, often has unclear underlying causes. However, it is widely recognized that the accumulation of estrogen and prostaglandins mediates inflammatory responses, leading to uterine ischemia and pelvic pain. Emerging evidence highlights the significant role of intestinal flora as a key regulator of circulating estrogens, linking it to estrogen-modulated diseases. Our laboratory previously demonstrated that sclareol effectively alleviates uterine proliferation and mitigates pain. Nonetheless, the relationship between sclareol's effects and gut microbiota modulation in dysmenorrhea remains unverified. To investigate this, we employed a mouse model induced with high doses of estradiol (1 mg/kg, IP) and administered sclareol (50 mg/kg, gavage) for five days. Fecal samples were subjected to 16S rDNA sequencing to analyze gut microbial composition. While no significant changes in alpha or beta diversity were observed, this study provides pioneering insights into sclareol's impact on specific gut microbiota. Notably, sclareol treatment increased the abundances of , , , and while reducing the abundances of and at the genus level. These effects may be associated with alterations in short-chain fatty acids, β-glucuronidase activity, and overall intestinal health. In conclusion, this study identifies sclareol as a potential functional food candidate for the prevention and management of estrogen-modulated diseases through gut microbiota modulation. Further research is warranted to elucidate the underlying mechanisms and therapeutic applications.
Bile acid is a responsible host factor for high-fat diet-induced gut microbiota alterations in rats: proof of the "bile acid hypothesis"
Watanabe M, Fujita Y, Hagio M, Ishizuka S, Ogura Y, Hayashi T, Fukiya S and Yokota A
High-fat diet (HFD)-induced alterations in gut microbiota may be associated with host pathophysiology, prompting increased interest in elucidating their causal relationships. However, the mechanisms by which HFDs induce these alterations require further clarification. Our previous study using cholic acid (CA)-fed rats suggested that bile acid drives the HFD-induced microbiota alterations as a host factor, a concept termed the "bile acid hypothesis". We analyzed the alterations in the cecal microbiota and bile acid composition in HFD-fed rats and compared the results with those of rats on a CA-supplemented diet. In both cases, the concentrations of total bile acids, including highly bactericidal deoxycholic acid (DCA), increased, concomitant with the increases in the Firmicutes (Bacillota)/Bacteroidetes (Bacteroidota) ratio. Operational taxonomic units (OTUs), accounting for 63.39% of the cecal microbiota of control rats, showed a significant correlation with the total bile acid concentration in HFD-fed rats. A DCA sensitivity test conducted in Firmicutes isolates, corresponding to the predominant OTUs from the HFD-fed rats, exhibited significantly higher DCA resistance compared with Bacteroidetes. The top 12 most abundant OTUs of Firmicutes and Bacteroidetes showing positive or negative correlations with the total bile acid concentration were selected from the HFD-fed rats, and their dynamics were compared with those in the CA-fed rats. Of the 24 OTUs, 18, which constituted 48.28% of the cecal population in the control rats, were altered in the same direction (increase or decrease) in the HFD- and CA-supplemented diet groups. Therefore, approximately half of the cecal populations in the control rats were affected by bile acids, substantiating the bile acid hypothesis microbiologically and quantitatively.
Formation of the intestinal microbiota during mouse weaning promotes maturation of the IgA repertoire after growth
Ando M, Kito I, Rachi T, Matsuda T and Oshima K
Secretory IgA (sIgA) is a class of antibodies that plays a pivotal role in mucosal immunity. The sIgA secreted into the intestinal tract acts to prevent luminal pathogens and food antigens from penetrating across the intestinal epithelial barrier, thereby contributing to the suppression of infections and food allergies. Furthermore, it binds extensively to symbiotic bacteria, exerting a significant impact on the gut microbiota. The antigen recognition specificity of antibodies is determined by the amino acid sequence of the variable region. Therefore, the type of IgA repertoire influences the formation and maintenance of the gut microbiota and susceptibility to infection and food allergy. The initial repertoire of IgA is induced by the extensive colonization of intestinal bacteria during the weaning period and is maintained for an extended period. However, the relationship between the initial gut microbiota and IgA repertoire development has yet to be fully analyzed. In the present study, the weaning gut microbiota was disrupted with antibiotics, and the IgA repertoire was subsequently analyzed in young adulthood. The administration of antibiotics during the weaning period resulted in the suppression of somatic hypermutation in the variable regions of IgA expressed in the small intestine, as well as an impact on multivalent reactivity in IgA during early childhood. Additionally, disturbances in the weaning gut microbiota led to alterations in the microbiota structure of adolescent mice. These findings suggest that the weaning gut microbiota plays a role in promoting the maturation of IgA function.