AGE/DOSE
Cancer

Promising New Study: Probiotics Significantly Reduce Colon Cancer Risk

Probiotics reduce precancerous lesions and cancer-associated cellular proteins in the colon of carcinogen-exposed rats.

By Bennett M. Sherman

Key Points

  • Probiotics prevent the buildup of abnormal, precancerous lesions in the colon called aberrant crypt foci.
  • Probiotics reduce oxidative stress —  damage to cells from deleterious, unstable molecules called free radicals — in the colon, which may suppress aberrant crypt foci.
  • At the cellular level, probiotics cut down colonic levels of a protein with elevated abundance in cancerous tissue — ꞵ-catenin — suggesting probiotics prevent colorectal cancer cell growth.

Aside from skin cancers, colorectal cancer is the third most common cancer type, accounting for an expected 52,550 deaths in the US in 2023. Researchers have attributed non-hereditary colorectal cancer onset to poor dietary choices and shoddy gut microbial composition, with increased abundance of detrimental gut bacterial species like Eschericia coli. Low-quality dietary choices and potentially harmful gut microbes induce inflammation from oxidative stress, precipitating cancer. Along those lines, identifying potentially beneficial bacteria (probiotics) along with natural compounds to prevent colorectal cancer onset has become crucial.

Published in Cancers, de Vasconcelos and colleagues from Federal University of Ceará in Brazil show that probiotics alone and with pterostilbene reduce the number of aberrant crypt foci that lead to cancer formation in colon tissue of rats treated with the carcinogen 1,2-dimethylhydrazine. Moreover, the probiotics and pterostilbene combination reduces levels of a molecular marker for oxidative stress, malondialdehyde, and increases the antioxidant glutathione. At the cellular level, probiotics alone or with pterostilbene diminish colon cell levels of a protein marker for cancer — ꞵ-catenin. These findings suggest that probiotics reduce the prevalence of aberrant crypt foci in colon tissue to prevent cancer and that, when combined with pterostilbene, can suppress colon oxidative damage.

Probiotics with Pterostilbene Reduce Oxidative Stress and Prevent Colorectal Cancer

To better understand whether supplementing with probiotics and/or pterostilbene affects colorectal cancer, de Vasconcelos and colleagues examined colon tissue aberrant crypt foci. After exposing rats to a cancer-inducing carcinogen, they found that deeper colonic segments from the stomach (medium and distal) as opposed to shorter depths (proximal) contained significantly more aberrant crypt foci after carcinogen treatments. Treating these rats with probiotics alleviated aberrant crypt foci accumulation in the medium and distal segments, while probiotics and pterostilbene diminished these foci only in the medium segment. These findings suggest that deeper colonic segments have higher numbers of carcinogen-induced aberrant crypt foci. Moreover, probiotic treatments ameliorated these foci, and the addition of pterostilbene didn’t have much of an effect.

Effects of Probiotics and Pterostilbene on Aberrant Crypt Foci. The illustration presents data on aberrant crypt foci numbers induced by the carcinogen 1,2-dimethylhydrazine (1,2-DMH) in different intestinal segments. Probiotics alone (PRO) show a significant reduction in aberrant crypt foci, while probiotics with pterostilbene (PS+PRO) reduce these abnormalities specifically in the medium intestinal segment. Statistical significance indicated by '#' (p < .05) compared to healthy Sham rats and '*' (p < .05) compared to 1,2-dimethylhydrazine (DMH) treatment.
(Barreira et al., 2023 | Cancers) Probiotics alone or with pterostilbene suppress numbers of aberrant crypt foci. The carcinogen 1,2-dimethylhydrazine (1,2-DMH) induced higher aberrant crypt foci numbers in the medium and distal intestines. Probiotics alone (PRO) significantly reduced these numbers, while probiotics with pterostilbene (PS+PRO) only reduced aberrant crypt foci in the medium intestinal segment. #= p < .05 compared to healthy Sham rats; *= p < .05 compared to 1,2-dimethylhydrazine (DMH) treatment.

To better grasp how probiotics influence oxidative stress, the Brazilian researchers examined malondialdehyde and glutathione levels in the colon. They found that the probiotics with added pterostilbene reduced malondialdehyde levels, a marker of oxidative stress. Furthermore, probiotics with pterostilbene significantly increased levels of the antioxidant glutathione. These findings suggest that probiotics and pterostilbene act synergistically to alleviate oxidative stress and promote higher antioxidant levels.

Effects of Probiotics and Pterostilbene on Oxidative Stress and Antioxidant Levels. Panel A depicts changes in colon malondialdehyde (MDA) levels: The carcinogen 1,2-DMH led to a doubling of MDA, which was significantly reduced by probiotics (PRO) and probiotics with pterostilbene (PS+PRO). Panel B illustrates antioxidant glutathione (GSH) levels: 1,2-dimethylhydrazine treatments lowered GSH levels, while probiotics with pterostilbene (PS+PRO) restored GSH levels.
(Barreira et al., 2023 | Cancers) Probiotics reduce the oxidative stress marker malondialdehyde (MDA), while probiotics with pterostilbene increase the antioxidant glutathione (GSH). A) The carcinogen 1,2-DMH almost doubled colon MDA levels, but probiotics (PRO) or probiotics with pterostilbene (PS+PRO) significantly cut down MDA levels. B) 1,2-dimethylhydrazine treatments reduced antioxidant GSH levels, but probiotics with pterostilbene (PS+PRO) restored GSH levels.

The Brazilian researchers sought to determine whether probiotics and/or pterostilbene reduce the number of colon cells that contain a protein marker for cancer — ꞵ-catenin. The researchers found that pterostilbene alone didn’t statistically reduce ꞵ-catenin but that probiotics alone and with pterostilbene did. These data show that probiotics alone and with pterostilbene reduce the accumulation of this protein marker for cancer, however, pterostilbene wasn’t necessary for this effect. Thus, probiotics can potentially slow cancer growth as shown by the reduction in the accumulation of ꞵ-catenin.

Modulation of Cancer Marker ꞵ-catenin by Probiotics and Pterostilbene. The graphic demonstrates the impact of the carcinogen 1,2-dimethylhydrazine (1,2-DMH) on ꞵ-catenin protein levels, leading to a dramatic increase. However, the introduction of probiotics alone or combined with pterostilbene results in a substantial reduction of ꞵ-catenin levels. While 1,2-DMH significantly elevates ꞵ-catenin (over threefold), probiotics with or without pterostilbene normalize ꞵ-catenin levels toward a near-normal state.
(Barreira et al., 2023 | Cancers) The carcinogen 1,2-dimethylhydrazine (1,2-DMH) dramatically increases the cancer protein marker ꞵ-catenin, but probiotics or probiotics with pterostilbene substantially reduce ꞵ-catenin levels. 1,2-DMH more than triples ꞵ-catenin levels, yet probiotics alone or with pterostilbene reduce ꞵ-catenin to near normal levels.

Identifying Optimal Probiotic and Pterostilbene Doses to Prevent Cancer

The study’s data provide evidence for using probiotics, like the one containing Lactobacillus acidophilus and Lactobacillus bifidum used in the study, to reduce colonic aberrant crypt foci and suppress potential colorectal cancer growth. Although adding pterostilbene to probiotics increased levels of the antioxidant glutathione, the results don’t show that the addition of pterostilbene reduced aberrant crypt foci numbers or inhibited levels of the protein marker for cancer — ꞵ-catenin. Thus, the study’s most significant findings were that probiotics can reduce aberrant crypt foci to potentially slow colorectal cancer growth in rats.

Future probiotics research should find what proportions of bacterial species work best to promote gut health and prevent colorectal cancer. Moreover, research should examine whether different pterostilbene dosages than the ones used in the study can work to prevent colorectal cancer on its own or synergistically when combined with probiotics. Although this study didn’t necessarily confirm a synergistic benefit of probiotics with pterostilbene, perhaps other pterostilbene dosages would improve probiotics’ effects on gut health.

Model and Dosage

Model: Male Wistar rats

Dosage: 1×109 CFU of probiotics daily and 15 to 30 mg/kg of pterostilbene daily

Source

Barreira MA, Campelo MWS, da Silva Martins Rebouças C, Duarte ASG, Barbosa MLL, da Cruz Fonseca SG, Queiroz RR, Holanda ÉU, de Vasconcelos ABA, de Sousa Araújo VJG, Diniz GM, Oriá RB, de Vasconcelos PRL. Pterostilbene and Probiotic Complex in Chemoprevention of Putative Precursor Lesions for Colorectal Cancer in an Experimental Model of Intestinal Carcinogenesis with 1,2-Dimethylhydrazine. Cancers (Basel). 2023 Apr 21;15(8):2401. doi: 10.3390/cancers15082401. PMID: 37190329; PMCID: PMC10136993.

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