Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy

Collimated Microbeam Reveals that the Proportion of Non-Damaged Cells in Irradiated Blastoderm Determines the Success of Development in Medaka (Oryzias latipes) Embryos

It has been widely accepted that prenatal exposure to ionizing radiation (IR) can affect embryonic and fetal development in mammals, depending on dose and gestational age of the exposure, however, the precise machinery underlying the IR-induced disturbance of embryonic development is still remained elusive. In this study, we examined the effects of gamma-ray irradiation on blastula embryos of medaka and found transient delay of brain development even when they hatched normally with low dose irradiation (2 and 5 Gy). In contrast, irradiation of higher dose (10 Gy) gamma-rays killed the embryos with malformations before hatching. We then conducted targeted irradiation of blastoderm with a collimated carbon-ion microbeam. When a part (3.8, 11 and 24%) (about 4, 10 and 25%) of blastoderm cells were injured by lethal dose (50 Gy) of carbon-ion microbeam irradiation, loss of about 10% or less of blastoderm cells induced only the transient delay of brain development and the embryos hatched normally, whereas embryos with about 25% of their blastoderm cells were irradiated stopped development at neurula stage and died. These findings strongly suggest that the developmental disturbance in the IR irradiated embryos is determined by the proportion of severely injured cells in the blastoderm

Oral rehydration solution normalizes plasma renin and aldosterone levels in patients with ulcerative colitis after proctocolectomy

Objectives: The possible effects and benefits of oral rehydration solution (ORS) on chronic dehydration after total proctocolectomy. Methods: To evaluate the effect of ORS on the renin-angiotensin system after remnant proctocolectomy in patients with ulcerative colitis (UC), we selected 20 patients after remnant proctocolectomy, ileal J pouch-anal anastomosis, and construction of a diverting ileostomy for UC. Patients were randomly divided into two groups, A (n=9) or B (n=11), 2 weeks after the surgery. In group A, ORS (1000 mL/day) was given for the first 7 days and mineral water (1000 mL/day) for the next 7 days. In group B, mineral water (1000 mL/day) was given for the first 7 days and ORS (1000 mL/day) for next 7 days. Plasma levels of renin, aldosterone and excretion of sodium in urine were evaluated at days 0, 7, and 14. We defined day 0 as the day of beginning this study. Results: Mean plasma renin levels on day 0 were six to eight times greater than the upper normal limit. In group A, ORS lowered plasma renin levels. In group B, plasma levels of renin and aldosterone after ORS were lower than those at days 0 and 7. Conclusions: ORS corrected increased plasma levels of renin and aldosterone to within the normal range in patients after proctocolectomy