The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development

Dai, Rui; Kelly, Bridget N.; Ike, Amarachi; Berger, David; Chan, Andrew; Drew, David A.; Ljungman, David; Mutiibwa, David; Ricciardi, Rocco; Tumusiime, Gerald; Cusack, James C.

doi:10.3390/cancers16030676

Cited by 8 publications

(5 citation statements)

References 117 publications

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“…Early-life exposures and subsequent lifestyle factors directly influence the gut microbiome. Exploring the interaction between these exposures, the gut microbiome, and early-onset colorectal cancer is challenging and further data collection is needed [10,32].…”

Section: Discussionmentioning

confidence: 99%

Early-Onset Colorectal Cancer—A Retrospective Study from a Tertiary Referral Hospital in Romania

Savu,

Șurlin,

Vasile

et al. 2024

Diagnostics

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Early-onset colorectal cancer emerges as a distinctive clinical and biological entity and is generally defined as the onset of colon or rectal neoplasia before the age of 50. Several reports describe an increasing incidence worldwide of colorectal cancers occurring in individuals younger than 50 years, along with particular histologic and molecular features. Although heredity may be an explanation in some cases with young-onset colorectal cancer, other driving factors remain partially unknown. The present study explores demographic, clinical, and pathological features within a group of patients diagnosed with colorectal cancer before the age of 50. It is a retrospective survey based on data collected between 2017 and 2023 within three surgical departments from a tertiary Romanian hospital. The clinical and pathological features we identified (later-stage disease, distal colon tumor localization, mucinous histology) are mainly superimposed with the existing data in the literature regarding this pathology. In order to lower the burden that colorectal neoplasia diagnosed in the young implies, a change of paradigm should be made in terms of establishing effective and targeted screening programs but also in the direction of enhancing complex clinical, pathological, and molecular diagnosis.

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Section: Discussionmentioning

confidence: 99%

Early-Onset Colorectal Cancer—A Retrospective Study from a Tertiary Referral Hospital in Romania

Savu,

Șurlin,

Vasile

et al. 2024

Diagnostics

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“…Taking into account the emergence of EOCRC, one could reasonably speculate that exposure to risk factors, such as a Western diet high in ultra-processed foods during childhood and adolescence, could contribute to increased incidence rates. Since a considerable time lapse is required for normal colonic mucosa to develop into cancer, significant physiological and metabolic disturbances beginning in early life may partially account for the rising incidence of sporadic EOCRC ( 23 , 26 ).…”

Section: The Influence Of Metabolic Syndromementioning

confidence: 99%

“…As we examine all age groups, a pattern of decreased microbial diversity and dysbiosis emerges as a common denominator in CRC risk. Pediatric studies hint at the early-life origins of dysbiosis as the setting for EOCRC development, linking it to factors like mode of delivery and antibiotic exposure during critical developmental periods ( 26 , 27 ). While causative links between EOCRC and microbiota remain elusive, studies establish a positive correlation between the use of anti-anaerobic antibiotics and colorectal cancer.…”

Section: The Influence Of Metabolic Syndromementioning

confidence: 99%

Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences

Atchade,

Williams,

Mermelstein

et al. 2024

Front. Public Health

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While advances in screening have resulted in declining rates of colorectal cancer (CRC) among adults ≥50 years of age since the mid-2000s, the incidence of early-onset CRC (EOCRC) has steadily increased over the last decade. This increase is not fully accounted for by hereditary factors, and the hypothesis that a sedentary lifestyle and obesity are the primary culprits is not fully supported by recent reports indicating that many affected individuals lead active lifestyles, maintain normal weight, and are otherwise healthy. Attention has shifted toward dietary patterns, notably the consumption of processed and ultra-processed foods found in Western diets, which are suspected of disrupting the gut microbiome balance that potentially leads to EOCRC. The impact of antibiotic use on the gut microbiome is also posited as a contributing factor, given its rising prevalence in medical and agricultural practices. We propose that a paradigm shift is necessary for EOCRC research, moving beyond metabolic factors to a broader exploration of dietary and microbial influences. Future research must prioritize understanding the relationship between dietary habits, particularly processed food intake, antibiotic exposure, and gut microbiome dynamics, to unravel the complex etiology of EOCRC. This will be crucial in developing comprehensive preventive strategies to address the increasing incidence of this malignancy in younger populations.

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“…The induction of inflammation is a contributor, either via direct or indirect methods, to promote the formation and progression of colorectal tumorigenesis. Both efforts to inhibit these inflammatory responses, as well as modulate bacteria within the gut microbiome, are currently under review as a means to reduce the formation of CRC [67][68][69][70][71].…”

Section: Microbiomementioning

confidence: 99%

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer

Jones,

Scheurlen,

Macleod

et al. 2024

Cancers

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Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including ‘EOCRC’, ‘obesity’, ‘obesity-related hormones’, ‘itaconate’, ‘adiponectin’, ‘leptin’, ‘M2a macrophage’, and ‘microbiome’. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.

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The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development

Cited by 8 publications

References 117 publications

Early-Onset Colorectal Cancer—A Retrospective Study from a Tertiary Referral Hospital in Romania

Early-Onset Colorectal Cancer—A Retrospective Study from a Tertiary Referral Hospital in Romania

Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer

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