Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy.

BACKGROUND: Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome-metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. METHODS: A case-control study was conducted. Cancer cases were recruited from Children's Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography-mass spectrometry approach. A multi-omics network integration program analyzed microbiome-metabolome pathways of PNS. RESULTS: Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies. CONCLUSIONS: Using multi-omics approaches, this study indicated specific microbiome-metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.

The association between the gut microbiome and fatigue in individuals living with cancer: a systematic review.

PURPOSE: Fatigue is the most distressing symptom for individuals with cancer. While numerous studies have investigated biological pathways that could underlie the mechanism of fatigue, the cause of fatigue remains unclear. This review aimed to investigate the association between gut microbial composition and fatigue in individuals with cancer. METHODS: Medline (PubMed), Embase (Elsevier), and CINAHL Complete (Ebscohost) were systemically searched on March 30, 2023, for articles investigating gut microbial composition (relative abundance, alpha diversity, and beta diversity) and fatigue in individuals with cancer; no limitations were placed on dates, participant age, nor cancer type/treatment. RESULTS: Microbial composition in the form of relative abundance was correlated with fatigue in six of the seven articles. A high relative abundance of g_Ruminoccocus was observed in individuals with low fatigue. An elevated relative abundance of g_Escherichia and f_Enterobacteriaceae was associated with high fatigue. However, other associations between fatigue and relative abundance composition, such as with g_Bifidobacterium and g_Faecalibacterium, had conflicting results. For alpha diversity and fatigue, the findings were contradictory; the association between beta diversity and fatigue was unclear due to conflicting results. CONCLUSIONS: Pro-inflammatory bacteria, such as f_Enterobacteriaceae, were more commonly associated with higher fatigue scores, while anti-inflammatory or short-chain fatty acid producing bacteria, such as g_Ruminoccocus, were linked with lower fatigue scores in individuals with cancer. The relationship between alpha and beta diversity and fatigue was inconclusive. Further investigation is needed to clarify whether gut microbial changes play a correlative or causal role in the development of fatigue in individuals with cancer.

A Pilot Study of the Gut Microbiota Associated With Depressive Symptoms and Sleep Disturbance Among Chinese and Korean Immigrants in the United States.

CONTEXT: Depression is prevalent among Asian Americans (AsA) during the COVID-19 pandemic, and depression often leads to sleep disturbance in this population. The gut microbiota (GM) plays a critical role in mental health and sleep quality, and the composition of the GM is largely unknown among AsA. OBJECTIVES: Examine associations of the GM with depressive symptoms and sleep disturbance among Chinese and Korean American immigrants. METHODS: Depressive symptoms (PROMIS Short Form-Depression) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were collected via surveys. PROMIS measure T-score > 55 indicates positive depressive symptoms, and a total PSQI score > 5 indicates sleep disturbance. 16S rRNA V3-V4 gene regions were sequenced from fecal specimens to measure GM. Permutational multivariate analysis of variance and linear discriminant analysis effect size were applied to examine associations of the GM with symptoms. RESULTS: Among 20 participants, 55% (n = 11) reported depressive symptoms and 35% (n = 7) reported sleep disturbance. A higher α-diversity was marginally associated with lower depressive symptoms: Chao1 (r = -0.39, p = 0.09) and Shannon index (r = -0.41, p = 0.08); ß-diversity distinguished participants between categories of depressive symptoms (weighted UniFrac, p=0.04) or sleep disturbance (Jaccard, p=0.05). Those with depressive symptoms showed a higher abundance of Actinobacteria, while those without depressive symptoms had a higher abundance of Bacteroidetes. No significant taxa were identified for sleep disturbance. CONCLUSIONS: Gut microbial diversity showed promising associations with depressive symptoms and sleep disturbance among Chinese and Korean immigrants. Specific taxa were identified as associated with depressive symptoms. Future studies with a larger sample size are warranted to confirm our findings.

Oral Microbiome, Mental Health, and Sleep Outcomes During the COVID-19 Pandemic: An Observational Study in Chinese and Korean American Immigrants.

COVID-19 is a systemic disease whose effects are not limited to the respiratory system. The oral microbiome (OM)-brain axis is of growing interest in understanding the broader, neuropsychiatric, impacts of the COVID-19 pandemic through a systems biology lens. In this context, mental health and sleep disturbance are often reported by Asian Americans. In a cross-sectional observational study design, we examined the associations of the oral microbiome with mental health among Asian Americans during the COVID-19 pandemic (between November 2020 and April 2021). Participants (n = 20) were adult Chinese and Korean American immigrants in Atlanta, Georgia, and primarily born outside the United States (60%) with a mean age of 34.8 years ±14 (standard deviation). Participants reported depressive symptoms, anxiety, and sleep disturbance, as measured by standard questionnaires. The OM was characterized by 16S rRNA V3-V4 gene using saliva. Depressive symptoms and anxiety were reported by 60% (n = 12) of participants, whereas 35% (n = 7) reported sleep disturbance. The α-diversity was significantly associated with depressive symptoms, and marginally with anxiety. Participants with depressive symptoms and anxiety had enriched Rothia and Scardovia, respectively, whereas those without symptoms had enriched Fusobacterium. Individuals with sleep disturbance had enriched Kingella. In conclusion, this study suggests significant associations of the OM diversity with certain mental health dimensions such as depressive symptoms and anxiety. Specific taxa were associated with these symptoms. The present observations in a modest sample size suggest the possible relevance of the OM-brain axis in studies of mental health during COVID-19.