In recent years, short-chain fatty acids (SCFAs) have been reported to play an important role in maintaining human health. Fecal SCFA concentrations correlate well with colonic SCFA status and gut microbiota composition. However, the associations with the gut microbiota functional pathway, dietary intake, blood SCFAs, and fecal SCFAs remain uncertain. To clarify these relationships, we collected fecal samples, blood samples, and dietary habit data from 12 healthy adults aged 22–51 years. The relative abundance of several SCFA-producing bacteria, gut microbiota diversity, and functional pathways related to SCFA biosynthesis were positively associated with fecal SCFAs even after adjusting for age and sex. Furthermore, fecal acetate was likely to be positively associated with serum acetate. By contrast, dietary intake was not associated with fecal SCFAs. Overall, the present study highlights the potential usefulness of fecal SCFAs as an indicator of the gut microbiota ecosystem and dynamics of SCFAs in the human body.

Sleep is essential for our health. Short sleep is known to increase disease risks via imbalance of intestinal microbiota, dysbiosis. However, mechanisms by which short sleep induces dysbiosis remain unknown. Small intestinal Paneth cell regulates the intestinal microbiota by secreting antimicrobial peptides including α-defensin, human defensin 5 (HD5). Disruption of circadian rhythm mediating sleep-wake cycle induces Paneth cell failure. We aim to clarify effects of short sleep on HD5 secretion and the intestinal microbiota. Fecal samples and self-reported sleep time were obtained from 35 healthy middle-aged Japanese (41 to 60-year-old). Shorter sleep time was associated with lower fecal HD5 concentration (r = 0.354, p = 0.037), lower centered log ratio (CLR)-transformed abundance of short-chain fatty acid (SCFA) producers in the intestinal microbiota such as [Ruminococcus] gnavus group (r = 0.504, p = 0.002) and Butyricicoccus (r = 0.484, p = 0.003), and lower fecal SCFA concentration. Furthermore, fecal HD5 positively correlated with the abundance of these genera and SCFA concentration. These findings suggest that short sleep relates to disturbance of the intestinal microbiota via decreased HD5 secretion.

A recent meta-analysis found that probiotics have moderate-to-large beneficial effects on depressive symptoms in patients with psychiatric disorders. However, it remains unclear how the baseline gut microbiota before probiotic administration influences the host’s response to probiotics. Therefore, we aimed to determine whether the predicted functional profile of the gut microbiota influences the effectiveness of probiotic treatment in patients with schizophrenia. A total of 29 patients with schizophrenia consumed Bifidobacterium breve A-1 (synonym B. breve MCC1274) for 4 weeks. We considered patients who showed a 25% or more reduction in the Hospital Anxiety and Depression Scale total score at 4 weeks from baseline to be “responders” and those who did not to be “non-responders”. We predicted the gut microbial functional genes based on 16S rRNA gene sequences and applied the linear discriminant analysis effect size method to determine the gut microbial functional genes most likely to explain the differences between responders and non-responders at baseline. The results showed that lipid and energy metabolism was elevated at baseline in responders (n = 12) compared to non-responders (n = 17). These findings highlight the importance of assessing the gut microbial functional genes at baseline before probiotic therapy initiation in patients with psychiatric disorders.

Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = − 0.307, p < 0.001). In β-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

Cancer is one of the most severe health problems worldwide accounting for the second leading cause of death. Studies have indicated that cancers utilize different metabolic systems as compared with normal cells to produce extra energy and substances required for their survival, which contributes to tumor formation and progression. Recently, the fruit fly Drosophila has been attracting significant attention as a whole-body model for elucidating the cancer mechanisms including metabolism. This tiny organism offers a valuable toolkit with various advantages such as high genetic conservation and similar drug response to mammals. In this review, we introduce flies modeling for cancer patient genotypes which have pinpointed novel therapeutic targets and drug candidates in the salivary gland, thyroid, colon, lung, and brain. Furthermore, we introduce fly models for metabolic diseases such as diabetes mellitus, obesity, and cachexia. Diabetes mellitus and obesity are widely acknowledged risk factors for cancer, while cachexia is a cancer-related metabolic condition. In addition, we specifically focus on two cancer metabolic alterations: the Warburg effect and redox metabolism. Indeed, flies proved useful to reveal the relationship between these metabolic changes and cancer. Such accumulating achievements indicate that Drosophila offers an efficient platform to clarify the mechanisms of cancer as a systemic disease.

Cancer burden has been increasing worldwide, making cancer the second leading cause of death in the world. Over the past decades, various experimental models have provided important insights into the nature of cancer. Among them, the fruit fly Drosophila as a whole‐animal toolkit has made a decisive contribution to our understanding of fundamental mechanisms of cancer development including loss of cell polarity. In recent years, scalable Drosophila platforms have proven useful also in developing anti‐cancer regimens that are effective not only in mammalian models but also in patients. Here, we review studies using Drosophila as a tool to advance cancer study by complementing other traditional research systems.