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.

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.