Open research questions in Gut microbiota and health
1,024 unresolved questions extracted from the limitations and future-work sections of 2,160 Gut microbiota and health papers in our library. Each links back to the study that raised it.
What the literature leaves open
RSV infection poses considerable challenges due to limited effective RSV-specific antiviral therapies. RSV infection can cause extensive metabolic disturbances in lung tissues.
Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Lonicerae japonicae Flos Against Respiratory Syncytial Virus · 2026 · DOILimited effective RSV-specific antiviral therapies. RSV infection can reduce gut microbial diversity and influence the development and progression of respiratory disease.
Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Lonicerae japonicae Flos Against Respiratory Syncytial Virus · 2026 · DOIThe study used a mouse model, - The sample size was limited to 55 mice, - The study did not investigate the long-term effects of pb2441, - The study did not compare pb2441 to other probiotics
Bacillus subtilis pb2441 partially attenuates hepatic steatosis with transcriptomic changes broadly similar to dapagliflozin in a Western diet mouse model · 2026 · DOIThe potential of probiotic-based approaches for NAFLD remains under investigation. Preclinical models of NAFLD do not fully recapitulate the complexity of human dietary patterns. There is a need for interventions that can improve systemic metabolic status while mitigating diet-driven hepatic steatotic changes.
Bacillus subtilis pb2441 partially attenuates hepatic steatosis with transcriptomic changes broadly similar to dapagliflozin in a Western diet mouse model · 2026 · DOIThe gap in understanding how Przewalski's gazelle adapts to dietary heterogeneity. The need to investigate mechanisms of adaptation to extreme environments.
Gut microbiota mediates dietary adaptation across spatially varying diets in the endangered Przewalski’s gazelle (Procapra przewalskii) · 2026 · DOIinvestigation of multilevel, precision-guided aging intervention strategies, - use of multi-omics technologies, AI-assisted analytical platforms, and rigorously designed clinical trials, - exploration of the paradigm shift from “delaying disease” toward “promoting healthy aging”
High-fructose diet–induced gut dysbiosis as a mechanistic driver of chronic inflammation and accelerated biological aging: a comprehensive review · 2026 · DOIExisting studies are substantially constrained by methodological limitations, - the majority of mechanistic evidence derives from germ-free animals, chronic stress models, fecal microbiota transplantation, and probiotic interventions, - these studies cannot be equated with the pathological mechanisms of human MDD, - the specific and direct etiology of depression has yet to be fully clarified, - no definitive pathogenic substances have been identified
Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota–Gut–Brain Axis’s Neural, Immune, and Metabolic Routes · 2026 · DOIResearch on the parallel relationship between characteristic microbiota and depressive symptoms, - elucidation of the mechanisms of the gut-brain axis, - exploration of the causal relationship between pathogenic and beneficial bacteria, - investigation of the specific and direct etiology of depression
Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota–Gut–Brain Axis’s Neural, Immune, and Metabolic Routes · 2026 · DOIEvaluation of the relationship between F. nucleatum and CRC progression, - Investigation of the mechanisms by which F. nucleatum promotes resistance to therapy, - Development of precision diagnostic and therapeutic approaches targeting F. nucleatum
From oral dysbiosis to colorectal cancer: reframing fusobacterium nucleatum as an oxidative stress-primed oncobion · 2026 · DOIClinical efficacy of microbiota-based therapies in RA remains uncertain, - Evidence from isolated case reports, animal studies, and small exploratory controlled studies are insufficient to establish the efficacy or safety of FMT in RA, - Limited direct effects on gut microbial composition have been observed with TNF inhibitors
Gut microbiota dysbiosis in rheumatoid arthritis: mechanisms linking intestinal barrier dysfunction to synovial inflammation · 2026 · DOIWell-designed randomized controlled trials are needed to establish the efficacy or safety of FMT in RA, - Further research is needed to understand the mechanisms linking gut dysbiosis to RA pathogenesis, - Investigation of the effects of microbiota-based therapies on gut microbial composition and immune homeostasis is required
Gut microbiota dysbiosis in rheumatoid arthritis: mechanisms linking intestinal barrier dysfunction to synovial inflammation · 2026 · DOIInvestigation of host and microenvironmental factors that may modify disease biology and treatment tolerance - Definition of nutritional status, fiber exposure, antibiotic use, fecal metagenomic function, circulating metabolites, and clinical endpoints in future trials - Direct lineage tracing and macrophage-specific receptor perturbation are needed
The gut-bone marrow axis in acute leukemia: an evidence-graded review of microbiota-immune crosstalk and therapeutic implications · 2026 · DOIOnly a subset of intestinal microorganisms can be cultivated under conventional laboratory conditions, - Bacterial recovery is highly dependent on aspiration techniques, transport conditions, culture media, incubation parameters, and laboratory expertise, - Contamination during sample collection remains a significant concern
Further clinical validation of multi-omics approaches is necessary, - Standardized methods for SB sampling and analysis need to be developed
The paper identifies a gap in the understanding of the implications of microbiome research for theological anthropology and spiritual practice. There is a need to reshape Christian conceptions of personhood, sacrament, and stewardship in light of emerging biomedical insights.
Further studies on the application of FMT in the treatment of pulmonary disease, - Investigation of the molecular mechanisms underlying the effects of gut microbiota on pulmonary diseases, - Exploration of the potential of CRISPR-Cas systems in restoring gut microbial balance
Current research has focused predominantly on autoantibody production, aberrant B-cell activation, and central neuroinflammatory processes - The factors associated with disease susceptibility, interindividual heterogeneity, and recurrence remain incompletely understood - AE-associated microbial signatures may be influenced by disease phase, treatment status, diet, sampling-related factors, and other sources of interindividual variation
Gut microbiota–neuroimmune crosstalk in autoimmune encephalitis: mechanistic insights and therapeutic prospects · 2026 · DOITargeting microbial metabolic function may more closely reflect the proposed mechanisms through which the gut microbiota influences immune regulation - Microbiota-derived metabolites, such as SCFAs, tryptophan, and bile acid metabolism, may be potential targets for future intervention
Gut microbiota–neuroimmune crosstalk in autoimmune encephalitis: mechanistic insights and therapeutic prospects · 2026 · DOIThe hologenomic regulatory networks integrating host genetic variation and microbial signals remain to be fully deciphered. The mechanisms underlying the complex trait of adipose deposition, shaped by both host genetics and environmental factors, including the gut microbiota, are not well understood.
Integrative hologenomic analysis reveals apolipoprotein D–associated host–microbe metabolic crosstalk linked to fat deposition in Jinhua pigs · 2026 · DOIThe role of miR-29a in shaping microbiota-driven bile acid metabolism is unclear. The impact of miR-29a deficiency on gut microbiota-bile acid homeostasis and the anti-inflammatory effects of LCA in colitis is not well understood.
MiR-29a deficiency disrupts gut microbiota-bile acid homeostasis and impairs the anti-inflammatory effects of lithocholic acid in colitis · 2026 · DOISmall sample size for Stage I (n=2), - Exclusion of patients with certain gastrointestinal disorders or history of gastrointestinal surgery, - Limited geographical representation (Northwest China)
Gut microbiota characteristics of gastric cancer patients across distinct pathological stages and their associations with tumor and paratumor mucosal microbiota · 2026 · DOIInvestigation of the mechanisms by which the gut microbiota influences gastric cancer progression, - Examination of the effects of dietary interventions on the gut microbiota in gastric cancer patients, - Expansion of the study to include larger and more diverse patient populations
Gut microbiota characteristics of gastric cancer patients across distinct pathological stages and their associations with tumor and paratumor mucosal microbiota · 2026 · DOIThe study faces the challenge of investigating the immunomodulatory effects of SSP1 in CTX-induced immunosuppressed mice. The study needs to assess the effects of SSP1 on gut microbiota composition and metabolic profiles. The study faces the challenge of demonstrating the alleviation of immunosuppression by SSP1 in a dose-dependent manner.
Immunomodulatory effects of Sanghuangporus sanghuang polysaccharide SSP1 in cyclophosphamide-induced immunosuppressed mice: associations with gut microbiota, short-chain fatty acids, and metabolic remodeling · 2026 · DOIThe effects of SSP1 on mucosal immunity and gut microbiota are unclear. There is a need to investigate the immunomodulatory activity of SSP1 in CTX-induced immunosuppressed mice. The study aims to fill this gap by assessing the effects of SSP1 on immune organ indices, histopathology, oxidative stress, splenocyte proliferation, and cytokine production.
Immunomodulatory effects of Sanghuangporus sanghuang polysaccharide SSP1 in cyclophosphamide-induced immunosuppressed mice: associations with gut microbiota, short-chain fatty acids, and metabolic remodeling · 2026 · DOIThe complexity of the intestinal microbial community and its role in feline diarrhea. The difficulty of establishing a suitable animal model for studying feline diarrhea. The need for a better understanding of the interactions between the gut microbiota and the host immune system.
Gram-Negative Bacterial Overgrowth Predominated by: Potential Association with Intestinal Barrier Impairment and Inflammatory Diarrhea in Cats · 2026 · DOI
Most-cited papers in Gut microbiota and health
- An obesity-associated gut microbiome with increased capacity for energy harvest · Nature · 2006 · 10,721 citations
- Structure, function and diversity of the healthy human microbiome · Nature · 2012 · 10,392 citations
- A human gut microbial gene catalogue established by metagenomic sequencing · Nature · 2010 · 10,011 citations
- Diet rapidly and reproducibly alters the human gut microbiome · Nature · 2013 · 9,048 citations
- Human gut microbes associated with obesity · Nature · 2006 · 7,737 citations
- Human gut microbiome viewed across age and geography · Nature · 2012 · 6,897 citations
- A core gut microbiome in obese and lean twins · Nature · 2008 · 6,781 citations
- Diversity of the Human Intestinal Microbial Flora · Science · 2005 · 6,599 citations
- Enterotypes of the human gut microbiome · Nature · 2011 · 6,431 citations
- A metagenome-wide association study of gut microbiota in type 2 diabetes · Nature · 2012 · 6,086 citations
Most recent work
- Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial · Nature Medicine · 2026
- Gut Microbiota-Derived Short-Chain Fatty Acids in Inflammatory Bowel Disease: Mechanistic Insights into Gut Inflammation, Barrier Function, and Therapeutic Potential · International Journal of Molecular Sciences · 2026
- Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial · Nature Medicine · 2026
- Imbalance in gut microbial interactions as a marker of health and disease · Science · 2026
- Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals · Nature Medicine · 2026
- Dietary polyphenols maintain human health through modulation of gut microbiota · Frontiers in Pharmacology · 2026
- The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases · Frontiers in Immunology · 2026
- Butyrate-Producing Bacteria as a Keystone Species of the Gut Microbiome: A Systemic Review of Dietary Impact on Gut–Brain and Host Health · International Journal of Molecular Sciences · 2026
- Personalized Nutrition Through the Gut Microbiome in Metabolic Syndrome and Related Comorbidities · Nutrients · 2026
- Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics · Journal of Advanced Research · 2026
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