Yuko Akagawa

Purpose: Cranberry juice is widely consumed to improve urinary health; however, its effects on the urinary microbiome (urobiome) of healthy individuals are unclear. We aimed to investigate the effect of continuous consumption of cranberry juice on the urobiome of healthy adults. Methods: This randomized, double-blind, placebo-controlled crossover trial included 40 healthy adults (21 women and 19 men) who completed the study. Participants consumed 80 mL of either cranberry juice or a placebo daily for 4 weeks, followed by a 4-week washout period and crossover to the alternate intervention. The urobiome was analyzed by 16S rRNA gene sequencing. Results: At baseline, the urobiome composition differed significantly between men and women (PERMANOVA, P = .015). Overall, alpha and beta diversities did not change significantly after either intervention. In women, cranberry juice consumption was associated with decreased relative abundance of the genus Lactobacillus (median: 28.4%-18.4%; P = .025); however, this change was not significant following correction for multiple comparisons (q = 0.25). No significant compositional changes were observed in men after the intervention. Conclusion: In this exploratory study, continuous cranberry juice consumption showed a potential to modulate the urobiome in a sex-specific manner. The observed trend toward decreased Lactobacillus abundance in women provides a basis for future, larger studies for validation and assessment of its clinical relevance for female urinary health.

Febrile urinary tract infection (fUTI) is common in infants, but specific risk factors for developing it remain unclear. As most fUTIs are caused by ascending infections of intestinal bacteria, dysbiosis—an imbalance in gut microbial communities—may increase fUTI risk. This study was conducted to test the hypothesis that abnormal development of gut microbiota during infancy increases the risk of developing fUTI. Stool samples were collected from 28 infants aged 3–11 months with first-onset fUTI (fUTI group) and 51 healthy infants of the same age (HC group). After bacterial DNA extraction, 16S rRNA expression was measured and the diversity of gut microbiota and constituent bacteria were compared between the two groups. The alpha diversity of gut microbiota (median Shannon index and Chao index) was significantly lower in the fUTI group (3.0 and 42.5) than in the HC group (3.7 and 97.0; p < 0.001). The beta diversity also formed different clusters between the two groups (p < 0.001), suggesting differences in their microbial composition. The linear discriminant analysis effect size showed that the fUTI group proportionally featured significantly more Escherichia-Shigella in the gut microbiota (9.5%) than the HC group (3.1%; p < 0.001). In summary, abnormal gut microbiota development during infancy may increase the risk of fUTI.

Approximately 10 Bifidobacterium species are known to inhabit the human intestinal tract. Bifidobacteria have been reported to possess a variety of probiotic benefits. However, when bifidobacteria are consumed internally as probiotics, the bacteria are killed by gastric acid. Therefore, we developed acid-resistant microcapsules containing Bifidobacterium breve M-16V and B. longum BB536, which are unaffected by gastric acid, and evaluated whether the microcapsule formulation increased the amount of bifidobacteria in the stool after administration compared with the powder formulation. The results revealed no significant difference in the percentage or number of B. longum between before and after administration of the powder or microcapsule formulation in children. By contrast, the bacterial count of B. breve was significantly increased after microcapsule formulation administration (1.5 × 10⁵ copies/g after administration versus 2.8 × 10⁴ copies/g before administration, p = 0.013). In addition, the increase in the bacterial count of B. breve in stools after administration of microcapsule formulation was approximately 1000-fold higher than that after powder formulation administration (p = 0.018). In conclusion, the results indicate that the microcapsule formulation is efficiently transferred to the large intestine without the adverse effects of gastric acidity in children.

Background: Children with severe motor and intellectual disabilities (SMIDs) frequently and continuously receive enteral nutrition and medications and lack adequate exercise, which may lead to dysbiosis, an imbalance in the composition of the gut microbiota. However, studies on the composition of gut microbiota in children with SMIDs are limited. Therefore, we aimed to examine the characteristics of the gut microbiota in children with SMIDs.Methods: 16S rRNA gene sequencing was performed using fecal samples of 10 children with SMIDs, who received enteral nutrition through a gastric fistula or gastric tube (SMID group: median age, 10.0 years), and 19 healthy children (healthy control [HC] group: median age, 9.0 years). Microbial diversity, microbial composition, and abundance of butyric acid‐producing bacteria were compared between the groups. Daily dietary fiber intake in the SMID group was evaluated using questionnaires.Results: The Shannon and Simpson indices (alpha diversity indices) were significantly lower in the SMID group than those in the HC group. Beta diversity analysis identified different clusters. Compared with the HC group, Clostridiales and butyric acid‐producing bacteria were less abundant and Bacteroidales were more abundant in the SMID group. Dietary fiber intake in the SMID group was approximately two‐thirds of the estimated average requirement for healthy Japanese children.Conclusion: Children with SMIDs showed dysbiosis with alteration in the microbial diversity, which could partly be attributed to their low dietary fiber intake. Further studies, with the intervention of prebiotics, probiotics, and synbiotics, are warranted to improve dysbiosis in children with SMIDs.

The gut microbiota was reported to differ between children with autism spectrum disorder (ASD) and typically developing (TD) children, and dysbiosis of the gut microbiota in preterm infants is common. Here, we explored the characteristics of gut microbiota in children born preterm with ASD. We performed 16S rRNA gene sequencing using stool samples from ASD children born preterm and TD children born preterm. Alpha diversity was significantly greater in the ASD group. A comparison of beta diversity showed different clusters. Linear discriminant analysis effect size analysis revealed significantly more Firmicutes in the ASD group compared with the TD group. In conclusion, the gut microbiota in children born preterm differs between children with ASD and TD.

腸内細菌叢はヒトの腸管内で一定のバランスを保ちながら共存している多種多様な細菌集団である．近年，遺伝子解析技術の進歩に伴い腸内細菌叢の研究が加速しヒトの健康に果たす役割の重要性が明らかとなってきた．特に小児期の腸内細菌叢の乱れ（dysbiosis）はその後の疾患発症のリスクを上昇させるため，dysbiosisの予防や是正は，生涯を通じた健康維持や促進につながる可能性がある．腸内細菌叢の形成に影響を与える様々な因子の中でも，抗菌薬投与が腸内細菌叢に及ぼす負の影響は大きい．そこで筆者らは抗菌薬の長期投与が乳幼児の腸内細菌叢に及ぼす影響を明らかにするため，有熱性尿路感染症の乳幼児を対象とした検討を行った．その結果，治療量のセフェム系抗菌薬の投与は腸内細菌叢の多様性を著明に低下させ，耐性のLactobacillales目が腸内細菌叢のほとんどを占めるようになること，しかし投与中止後1–2か月で多様性は回復すること，その後少量の予防量（0.2 g/日）のST合剤の持続投与を行っても多様性は乱されず，腸内細菌叢に及ぼす影響は小さいことが明らかとなった．そしてST合剤の少量持続投与中，尿路感染症の起因菌が属するEnterobacteriales目の構成割合が抑制されていたことから，ST合剤の少量持続投与は有熱性尿路感染症の再発予防に有効かつ安全な治療であると考えられた．

Neonatal jaundice, caused by excess serum bilirubin levels, is a common condition in neonates. Imbalance in the gut microbiota is believed to play a role in the development of neonatal jaundice. Thus, we aimed to reveal the gut microbiota characteristics in neonates with jaundice. 16S rRNA gene sequencing was performed on stool samples collected on day 4 from 26 neonates with jaundice (serum total bilirubin > 15.0 mg/dL) and 17 neonates without jaundice (total serum bilirubin < 10.0 mg/dL). All neonates were born full term, with normal weight, by vaginal delivery, and were breastfed. Neonates who were administered antibiotics, had serum direct bilirubin levels above 1 mg/dL, or had conditions possibly leading to hemolytic anemia were excluded. The median serum bilirubin was 16.0 mg/dL (interquartile range: 15.5–16.8) and 7.4 mg/dL (interquartile range: 6.8–8.3) for the jaundice and non-jaundice groups, respectively. There was no difference in the alpha diversity indices. Meanwhile, in the jaundice group, linear discriminant analysis effect size revealed that Bifidobacteriales were decreased at the order level, while Enterococcaceae were increased and Bifidobacteriaceae were decreased at the family level. Bifidobacteriaceae may act preventatively because of their suppressive effect on beta-glucuronidase, leading to accelerated deconjugation of conjugated bilirubin in the intestine. In summary, neonates with jaundice had dysbiosis characterized by a decreased abundance of Bifidobacteriales.

Butyric acid produced in the intestine by butyric acid-producing bacteria (BAPB) is known to suppress excessive inflammatory response and may prevent chronic disease development. We evaluated whether fiber-rich barley intake increases BAPB in the gut and concomitantly butyric acid in feces. Eighteen healthy adults received granola containing functional barley (BARLEYmax^®) once daily for four weeks. Fecal DNA before intake, after intake, and one month after intake was analyzed using 16S rRNA gene sequencing to assess microbial diversity, microbial composition at the order level, and the proportion of BAPB. Fecal butyric acid concentration was also measured. There were no significant differences in diversities and microbial composition between samples. The proportion of BAPB increased significantly after the intake (from 5.9% to 8.2%). However, one month after stopping the intake, the proportion of BAPB returned to the original value (5.4%). Fecal butyric acid concentration increased significantly from 0.99 mg/g feces before intake to 1.43 mg/g after intake (p = 0.028), which decreased significantly to 0.87 mg/g after stopping intake (p = 0.008). As BAPB produce butyric acid by degrading dietary fiber, functional barley may act as a prebiotic, increasing BAPB and consequently butyric acid in the intestine.

Background This study aimed to test the hypothesis that reduced urinary excretions of neutrophil gelatinase-associated lipocalin (NGAL) predispose children to recurrence of febrile urinary tract infection (fUTI). Methods Subjects were 38 children diagnosed with fUTI. To examine risk factors for recurrence of fUTI, the subjects were divided into a non-recurrent group and a recurrent group according to the presence or absence of fUTI over 3 years since the first episode. We measured the urinary NGAL levels in patients with fUTI at the non-infected stage in addition to age-matched healthy control children. Results In a multiple logistic regression analysis, significant differences between the groups were not observed for age, sex, the prevalence of kidney scarring and bladder bowel dysfunction, urinary β2-microglobulin/creatinine (Cr) level, and serum levels of Cr and Cystatin C, while the recurrent group had significantly more cases with grade III or higher vesicoureteral reflux (p < 0.01). Furthermore, the urinary NGAL/Cr in the recurrent group (median, 3.60 μg/gCr) was significantly lower than that in the non-recurrent group (median, 16.47 μg/gCr; p < 0.01), and age-matched healthy control children (median, 14.14 μg/gCr; p < 0.05). The area under the receiver operating characteristic curve of NGAL/Cr was 0.86 for predicting recurrence of fUTI. A cut-off value of 11.59 μg/gCr had the best accuracy to predict recurrent fUTI yielding a specificity of 78% and a sensitivity of 93%. Conclusions Reduced levels of urinary NGAL, which protects against urinary infection, are a risk factor for recurrence of fUTI and could serve as a biomarker.

Background In Japan, the use of desmopressin (1-desamino-8-D-arginine vasopressin) is only recommended for nocturnal enuresis with unconcentrated first morning urine, which suggests a relative deficiency of antidiuretic hormone secretion during sleep. However, no such limitations have been described in a standardization document of the International Children's Continence Society. We aimed to determine whether desmopressin treatment induces any response in nocturnal enuresis with concentrated first morning urine. Methods Outpatients aged 6-15 years who exhibited monosymptomatic nocturnal enuresis were examined. Data were obtained from 41 treatment-naive patients (median age 9.7 years) with nocturnal enuresis, who received desmopressin as their first line of treatment. The patients were divided into two groups demonstrating unconcentrated (osmolality < 800 mOsm/L, Low-Osm group) and concentrated (osmolality >= 800 mOsm/L, High-Osm group) first morning urine, respectively; we compared the response to desmopressin treatment between the groups at 1 month after the administration or updosing of desmopressin; responses were defined as partial or complete according to the International Children's Continence Society standards. Mann-Whitney U-tests or Fisher's exact tests were used for analysis. Results The Low-Osm (median age 9.6 years) and High-Osm groups (median age 9.7 years) had 14 and 27 patients, respectively; the response rates to desmopressin treatment were 64.3% and 59.2%, respectively, indicating no significant differences (P = 0.99). Conclusion Desmopressin treatment may be a feasible option for treating nocturnal enuresis with concentrated first morning urine.