Dietary intervention reduces cancer treatment-related symptoms and toxicity

Modern chemotherapy , Radiotherapy destroys cancer cells while , It also causes damage to healthy cells , Cause related toxicity , Reactions such as constipation , diarrhea , fatigue , nausea , Vomiting, etc .

Cancer patients Nutritional status May be cancer treatment-related toxicity Core determinants , It is also an indicator of cancer symptoms .

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Some preclinical studies and preliminary clinical trials have shown that , Diet intervention May be reduce some cancer Treatment related Symptoms and toxicity . Possible mechanisms include impacts inflammation 、 Oxidative stress 、 Muscle mass 、 Heart health and Regulate intestinal flora .

This chapter covers three major parts , Include ：

• Diet pattern ： Mediterranean diet 、 Periodic fasting 、 There are three ketogenic diets
• Dietary composition ： Fruits and vegetables 、 Fish oil 、 Dietary fiber, etc
• Effect of intestinal flora on cancer treatment-related symptoms 、 Toxicity and effects

Alan J. Kim et al.,Cancer Treatment Reviews, 2022

01
Diet pattern

The Mediterranean diet

The Mediterranean diet , It is characterized by a large intake of fruit 、 vegetables 、 peas and beans 、 olive 、 Whole grain 、 Unsaturated fat 、 Nuts and fish ; Moderate drinking ; Reduce red and processed meat and high-fat dairy products , Yes Reduce inflammation , Improve cardiovascular health , Anti obesity , Improve blood fat as well as For intestinal flora and immune regulation Yes positive effect .

↓↓ Reduce sudden cardiac death

In a large prospective study , Investigated hormone replacement therapy 、 Calcium and vitamins D Or the effect of dietary adjustment on healthy postmenopausal women , Discover Mediterranean dietary patterns and Reduce sudden cardiac death Related to the risk of .

↓↓ Relieve cancer-related fatigue

In a randomized controlled trial ,23 Men with prostate cancer received at least 3 Months of androgen deprivation therapy , Were randomly divided into two groups , A group accepts 12 Weekly routine treatment , The other group received a Mediterranean diet and six personalized nutrition consultations at the same time , Compared with conventional treatment , Stick to the Mediterranean diet and Relieve cancer-related fatigue as well as Improve the overall quality of life of .

↓↓ Relieve the symptoms of gynecological tumor patients

One is right 22 An observational study of gynecological cancer patients receiving platinum chemotherapy showed that , Patients who stick to the Mediterranean diet Less gastrointestinal toxicity , nausea 、 Have a stomachache 、 The frequency and severity of abdominal distension and interference with daily activities were statistically significant .

Periodic fasting

Periodic fasting is Do not eat food or drink other than water partially or completely for a given period of time . In animal models and human patients , Periodic fasting is closely related to the reduction of toxicity in cancer treatment .

↓↓ Delay tumor progression

for example , In a preclinical study , Fasting conditions increase sensitivity to chemotherapeutic drugs , and Delayed tumor progression . Others have found that , In a mouse model of hormone receptor positive breast cancer , Periodic fasting or a diet similar to fasting (FMD) can Enhance the activity of hormone therapy ( Such as tamoxifen and fluvistrom ), And pass Reduce Circulating insulin 、 Leptin and IGF1 Level and inhibition AKT-mTOR Signal transmission Promote long-term tumor regression .

↓↓ Improve the quality of life

In one, for 131 name HER2 Negative II/III Patients with stage breast cancer II Phase I clinical studies have confirmed 4 God FMD The potential benefits of . Before neoadjuvant chemotherapy 3 Days and the day of neoadjuvant chemotherapy , Accept the vegetal 、 Low amino acid replacement diet （ Including broth 、 soup 、 Liquid 、 Vitamin tablets and tea ） Of patients reported that , And the control group ( A regular diet ) comparison , Overall well-being improved , mood 、 The body 、 Cognitive and social functions have improved .

↓↓ Reduce chemotherapy-related toxicity

In a controlled crossover pilot study , A survey of 30 Gynecological cancer patients receiving chemotherapy , It turns out that , An improved form of short-term fasting Reduced chemotherapy-related toxicity , Including stomatitis 、 Have a headache 、 Weakness and overall toxicity .

As report goes ,FMD It is safe and feasible , Sure Reduce fat , Reduce circulating insulin growth factor 1、 Insulin and leptin levels . fasting Strongly affects metabolism and cellular pathways , Causes circulating insulin-like growth factor 1 (IGF-1) And glucose levels falling . These changes in turn affect several oncogenes , Include RAS and AKT The signal is connected road , Results in down regulation of cell growth and proliferation .

Fasting and FMD( Low calories 、 A low protein and low sugar diet ) It may be related to reducing the side effects of chemotherapy , That is, when nutrients are deficient , Normal cells , Not tumor cells , It can be switched to the protective mode of inhibiting the growth and proliferation pathways , This process is called Differential stress resistance .

↓↓ Enhance immunity

Besides , Fasting and / or FMD It has been proved that Strengthen the immune system , Reduce inflammation , Slow down the loss of bone mineral density in mice , And reduce HER2 Negative II Chemotherapy induced lymphocytes in patients with stage breast cancer DNA Damage .

Ketogenic diet

Ketogenic diets are usually characterized by Low carbohydrate consumption , Of total daily calorie intake 5%-10%, But other energy producing nutrients in large quantities , That is, the contents of fat and protein are different . Ketogenic ratio is used to define the ketogenic capacity of a diet , It is defined as the ratio of grams of fat to the sum of grams of carbohydrate and protein .

The ketogenic diets most studied in cancer include Classic ketogenic diet (CKD), It is characterized by a ketone production ratio of 4：1 or 3：1, everyday 87%-90% Calories come from fat ) and Medium chain triglyceride ketogenic diet [MCTKD, among 30%-60% Total calories come from medium chain fatty acids , Such as caproic acid (C6)、 bitter (C8)、 Sunflower acid (C10) And lauric acid (C12)].

↓↓ blood sugar , Weight is more controllable , High quality of life

In patients with glioblastoma who have received radiotherapy, chemotherapy and adjuvant chemotherapy , Those with ketogenic diets Low blood sugar levels For patients on a standard diet . Some studies have found that , In patients with non metastatic breast cancer who receive radiotherapy , A ketogenic diet based on natural foods is compared to an unspecified standard diet , Lose more weight and fat , Higher quality of life .

↓↓ Reduce cancer treatment-related toxicity

The mechanism by which ketogenic diets reduce cancer treatment-related toxicity can be used Watson effect （Warburg effect） To explain , In the Waals effect , Cancer cells utilize glycolysis rather than oxidative phosphorylation , can The prevention of Caused by reactive oxygen species Oxidative damage .

Ketogenic diet （ It is usually high in fat and low in glucose ）, This metabolic difference can be exploited , or Starving cancer cells , or Forcing them to switch to oxidative phosphorylation . Compared with normal cells , Increased oxidative stress in cancer cells can make them more sensitive to chemotherapy and radiation , thus Reduce the dose required for treatment , Reduce treatment-related toxicity .

↓↓ Pay attention to the side effects of high-fat ketogenic diet

Limited evidence supports the use of ketogenic diets in clinical practice , and , According to the total content and relative macronutrient composition , Different types of The ketogenic diet may have treatment-related toxic side effects Produce different shadows ring . for example , Long term consumption of high-fat ketogenic diet may increase the risk of cardiovascular or cerebrovascular diseases , Especially when used in combination with specific anticancer drugs . A high-fat ketogenic diet may also Increases the risk of severe steatohepatitis , Promote the progress of liver fibrosis . Besides , Studies have shown that , A high-fat ketogenic diet increases the circulating level of ketoacetate , It also promoted the expression of BRAF-V600E Oncogenic human melanoma cells have tumor growth potential .

therefore , According to the current understanding of nutrition , The diet of patients receiving cancer treatment should include all macronutrients , To reduce the risk of malnutrition .

02
Dietary composition

Dietary fiber

Dietary fiber is associated with gastrointestinal toxicity and symptom prevention in a variety of tumor types . In a randomized controlled trial , Take a high dose of dietary fiber during radiotherapy (18 g / God ) Of patients with pelvic cancer report radiation-induced The incidence of gastrointestinal toxicity is low , It is proved that dietary fiber has potential effect in preventing radiation therapy related toxicity .

Dietary fiber is OK Promote healthy intestinal flora , Thus reducing toxicity and Enhance the therapeutic effect , For example, fiber is related to the immune promoting Clostridium pratense and short chain fatty acid butyrate . It has been found that in patients with melanoma , Dietary fiber can affect the intestinal flora , And with Enhancement of immune checkpoint blocking response of .

Spencer CN, et al.,Science. 2021

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about Peritoneal carcinoma 、 Progression of colon cancer or primary gastric cancer Of the patients , You may need to Low dietary fiber diet , To reduce the risk of intestinal obstruction .

Fruits and vegetables

Increase the intake of fruits and vegetables Improve the physical and cognitive function of gastric cancer survivors 、 Reducing fatigue is related to loss of appetite .

Fruits and vegetables contain too much Phytochemicals , And the effects of several phytochemicals have been examined , It is summarized in the table below .

Alan J. Kim et al.,Cancer Treatment Reviews, 2022

for example , The antioxidant and anti-inflammatory effects of grape products are attributed to their phytochemicals , Namely stilbene 、 Anthocyanins and procyanidins , Include Resveratrol .

Several other fruits , Including blackcurrants 、 Plum 、 Pomegranates and apples , Has been proven to have Anticancer and cytotoxic effects , This is due to phytochemicals , Especially polyphenols and flavonoids Antioxidant and anti-inflammatory effects .

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about The risk of intestinal obstruction is higher Of patients , Should be Avoid excessive intake Dietary fiber related to fruits and vegetables .

Phytochemicals

As report goes , stay 70 A phytochemical found in many plants Resveratrol Sure Increase the sensitivity of colorectal cancer cell lines to chemotherapy drugs , Including adriamycin 、 Sorafenib 、5- Fluorouracil 、 Etoposide 、 Mitomycin 、 Oxaliplatin and curcumin .

Resveratrol is introduced in detail in this article ：

How to regulate intestinal flora ？ Common natural substances 、 probiotics 、 Introduction of prebiotics

Be careful ： High dose ( Every day >2.5 g ) Can cause Mild toxicity ( Including diarrhea 、 Gastrointestinal symptoms and forehead headache ), Even in healthy people .

Other polyphenols May also have Anti inflammatory and antioxidant effects .

▸ quercetin It is a common flavonol in berries , It acts on inflammatory mediators , Including interleukin 6、 Interleukin 8、 interferon γ、 Inducible nitric oxide synthase 、 Cyclooxygenase 2 And tumor necrosis factor α To induce anti-inflammatory effects , And in cancer cell lines sensitive to pro apoptotic stimuli Pro apoptotic effect .

▸ Fisetin It is a kind of strawberry 、 Flavonoids in apples and persimmons , Structurally similar to quercetin , Have a similar Anti inflammatory and anticancer activity .

▸ Lycopene It's tomatoes and red fruit （ Including papaya and watermelon ） A phytochemical in , have High antioxidant activity , And by reducing oxidative stress and chromosomal and membrane abnormalities Reduce carcinogenic damage . Besides , Lycopene has Neuroprotective effect , And is considered to be able to pass Reduce oxidative stress and neuroinflammation To prevent neurotoxicity .

tea

A cup of tea , In especial Green tea , And Anticancer effect 、 Reduce drug-induced toxicity and sensitivity to chemotherapy drugs of .

↓↓ Inhibit secondary tumors

There is in tea Catechins It plays an important role in promoting health . Epigallocatechin gallate In vitro and in vivo breast cancer models Antioxidant and anti-inflammatory activity ( Especially in the case of oxidative stress induced by tamoxifen ), can Inhibition Of patients with head and neck or pelvic cancer Radioactive dermatitis , and Inhibition Secondary tumor Secondary development .

↓↓ Prevent adverse reactions caused by radiation

As report goes , Epigallocatechin gallate can also be used in The prevention of Exposure to γ After radiation or cisplatin based therapy Dysfunction of salivary gland cells , prevent Adverse hematological changes caused by radiation ( Like anemia 、 Thrombocytopenia ), as well as The prevention of Caused by bleomycin Pulmonary fibrosis .

↓↓ Reduce drug-induced toxicity

Besides , Epigallocatechin gallate can Reduce Gastrointestinal disorders during irinotecan treatment 、 Caused by cisplatin Nephrotoxicity and ototoxicity , And doxorubicin and daunorubicin treatment Cardiotoxicity .

In terms of drug sensitization , Green tea shows a lot to do with chemotherapy Synergy , Some of them are related to 4- Hydroxytamoxifen Combined use can increase the level of cytotoxicity , By lowering the large B Cell lymphoma (Bcl-xL) gene ( Encoding anti apoptotic protein ) The expression of makes MCF7 Cell pair 5- Fluorouracil sensitization , as well as 4 Only inoculate T1 Of Balb/c The sensitivity of mice to paclitaxel . This sensitization is achieved by Reduce The dosage of chemotherapy drugs required It effectively reduces the severity of drug-induced toxicity .

dairy / Milk fat

dairy / The relationship between dairy products and cancer treatment has been controversial . Although it is reported that Balb/c In mice , dairy / Milk fat can Enhance the effectiveness of paclitaxel treatment , and Reduce Related to the preparation toxicity , for example , Organ damage 、 Gastrocnemius muscle loss 、 Epididymal adipose tissue decreases 、 Red and white blood cell loss and jejunal morphology 、 Villi length and intestines γ- Destruction of glutamyltranspeptidase activity .

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There are studies that show that , Among women diagnosed with early invasive breast cancer , High fat milk And breast cancer 、 All cause and non breast cancer An increase in mortality , And the association with the progression of breast cancer in premenopausal women Increased risk of .

fish oil

Fish oil is rich in omega-3 Fatty acids , Such as eicosapentaenoic acid (EPA) And docosahexaenoic acid (DHA), Its role in reducing cancer and cancer treatment-related symptoms and toxicity has been widely studied .

↓↓ Reduce the toxicity caused by chemotherapy

A randomized clinical trial showed that , In patients with cervical cancer (n=40) in , Replenishing fish oil can Reduce the toxicity caused by chemotherapy , Like anorexia 、 nausea 、 Dry mouth and taste disorders . One is right 88 Patients with cancer were supplemented with arginine 、 Studies of glutamic acid and fish oil show that , Supplement arginine 、 Glutamic acid and fish oil can significantly Reduce 3-4 Grade I hematotoxicity , and Improve the two-year overall survival rate .

↓↓ Enhance the anti-tumor effect

Some in vitro and in vivo studies have shown that , Compared with chemotherapy alone , Given during chemotherapy EPA and DHA Sure Enhance the anti-tumor effect , Reduce the toxicity of chemotherapy to normal tissues , Inhibit systemic inflammation , Improve the nutritional status of cancer patients . Again , In paclitaxel and cisplatin / During carboplatin treatment , Add... To your equal calorie diet EPA With patients with non-small cell lung cancer Reduced fatigue 、 Improved appetite And chemotherapy Decreased neuropathy of .

↓↓ omega-3 Fatty acids reduce the toxicity of chemotherapy

omega-3 Fatty acids are OK Reduce cancer-related cachexia , Increase immune regulation , So as to enhance chemotherapy and radiotherapy for patients with colorectal cancer and esophageal cancer , Reduce Caused by chemotherapy in patients with esophageal cancer toxicity （ Such as stomatitis ,3/4 Grade 1 diarrhea , And elevated levels of aspartate aminotransferase and alanine aminotransferase ）.

Various mechanisms have been proposed to explain omega-3 The role of fatty acids in reducing cancer treatment-related toxicity . One assumption is that Composition of cell membrane , This indicates that unsaturated fatty acids are incorporated into the cancer cell membrane , This results in a different pattern of cell membrane composition from that of normal cells . Considering that the cell membrane is the center of intracellular signal transduction and gene expression regulation , Between cancer cells and normal cells Different distribution of fatty acids on cell membrane May lead to Signaling pathways Different activation ( for example ,PKC Activate and NF-KB access ).

Even though omega-3 Fatty acids have shown benefits in clinical trials , But in preclinical models ,omega-3 Fatty acid sixteen carbon -4,7,10,13- Tetraenoic acid has been shown to Inhibition of tumor directed cytotoxicity of platinum compounds , This may cause potential harm to the patient .

therefore , Before recommending fish oil for clinical use , It is necessary to further study the composition and purification of common fish oil EPA/DHA Effects on the cytotoxicity of specific chemotherapeutic drugs .

Curcumin and turmeric

Turmeric is a kind of Flowering plants , Can be extracted from Curcumin . They are related to the prevention and treatment of adverse events related to chemotherapy and radiotherapy . Turmeric / The beneficial effects of curcumin on cancer are attributed to their Antioxidant and anti-inflammatory properties , And they are Inhibit cell proliferation and cancer stem cell development The role of , And they Positive effect on intestinal flora and immune system effect .

↓↓  Ginger butter reduces chemotherapy 4 Incidence of grade I toxicity

Turmeric oil has Liver protecting effect , and relieve Concanavalin A Induced Oxidative stress and inflammation , So as to reduce the multiple symptoms and toxicity of human patients . Again , And other herbal substances ： Fermented soybean extract 、 Green tea extract 、 Mycelia of Coriolus cinnamomi 、 Spirulina combined with grape seed extract , can Significantly reduce the Receive calcium folinate /5- Fluorouracil Of chemotherapy patients 4 Incidence of grade I toxicity .

↓↓  Turmeric / Curcumin reduces the severity of mucositis

One assessment concluded that , Topical application of turmeric and curcumin can Control receiving chemotherapy and / Or oral mucositis in cancer patients treated with radiotherapy , And accept turmeric / Curcumin treated patients reported Less pain , Erythema intensity The lower , Ulcer area Less . An assessment 32 A clinical trial of patients with head and neck cancer who received radiotherapy also concluded , Oral nano micellar curcumin Significantly reduce Of mucositis caused by radiotherapy severity .

↓↓  Turmeric / Curcumin helps control cancer-related pain

A multicenter clinical trial in postmenopausal patients with breast cancer (n=45) Show , Combined application of hydroxytyrosol ( A phenolic phytochemical found in olive oil that has strong antioxidant activity )、omega-3 Fatty acids and curcumin Sure reduce Patient reported Pain , and Reduce inflammation biomarkers The level of .

↓↓  The synergy between turmeric and common chemotherapy drugs / Antagonism

Curcumin in I In the phase of clinical trial Synergistic enhancement of chemotherapeutic drugs FOLFOX(5- Fluorouracil 、 Calcium folinate 、 Oxaliplatin ) With dasatinib FOLFOX To deal with the HCT116 and HT-29 Cells have Anti proliferation effect .

Although these results suggest promising areas for further research , But for human breast cancer cell lines ( namely MCF-7、MDA-MB-231 and BT-474) In vitro experiments showed that , Curcumin And with Irinotecan or cyclophosphamide Based chemotherapy exists between Antagonism , Dietary supplements of curcumin may Inhibition Chemotherapy based tumor regression . These findings indicate that , More research is needed to determine whether patients with breast cancer should avoid curcumin supplementation during chemotherapy .

Other dietary ingredients ( selenium 、 glutamine )

Glutamine is macrophage 、 The main fuel source of lymphocytes and intestinal cells , It has many beneficial effects , Include Improve the immune system 、 Reduce inflammation and decompose stress state .

↓↓ Chemotherapy combined with glutamine supplement , Reduce the incidence of hematological toxicity

A randomized study of cancer patients receiving concurrent chemoradiotherapy showed that , In addition to the regular diet , And accept Arginine 、 Glutamine and fish oil supplements Of patients compared with patients who did not receive supplements , happen 3 Grade or 4 The incidence of grade I hematological toxicity is low .

↓↓ Selenium supplements improve the immune system

As report goes , Selenium supplementation has Antioxidation , Stimulate the cytotoxic activity of natural killer cells , Reduce tumor angiogenesis , And improve the immune system in vitro . Selenium is related to the detoxification of heavy metals . These effects may occur because selenium is an important component of selenoproteins and enzymes , These selenoproteins and enzymes help Antioxidant defense 、 Reduce inflammation 、 Thyroid hormone production 、DNA synthesis .

A review of articles on selenium and radiotherapy , The conclusion is that , Take daily 300-500 Micrograms of selenium , continued 10 Day to 6 Months , Sure Reduce the side effects of radiotherapy , Including diarrhea 、 Salivary gland injury and radiation wound , No adverse effects .

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High doses of selenium (>400 MCG / God ) Can cause serious side effects , Like brittle nails 、 Alopecia 、 Gastrointestinal dysfunction 、 Rash 、 Nervous disorders, etc .

Vitamin and mineral supplements

Vitamin supplements in Reduce cancer and cancer treatment-related symptoms and toxicity Studies on the efficacy of these drugs have shown conflicting results .

for example , Although many studies have shown that vitamins C Supplements have Potential anticancer and toxic effects , But vitamins for cancer patients undergoing chemotherapy C The systematic review conducted found that , There is no clear evidence Indicates taking vitamins C Supplements can reduce toxicity or improve the anticancer effect of treatment .

Again , Although vitamins D Supplements have been shown to Prevent bone loss caused by cancer treatment , And restore vitamins experienced by many patients with early breast cancer D Insufficient , But vitamins reported in various studies D The anti-tumor effect of is still very poor .

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Because the effect of vitamin supplements during cancer treatment is not clear , Patients are strongly advised to follow dietary recommendations , Take vitamins from natural foods such as fruits and vegetables , Instead of relying on dietary supplements .

03
Intestinal flora

Intestinal flora and cancer

The complex microbiota in the gastrointestinal tract of a healthy human has shown significant physiological benefits , Such as Enhance intestinal function and digestive capacity 、 Resist pathogens and regulate immunity .

although “ health ” The definition of intestinal flora is not clear , But the data show that , have Diversification of high functional redundancy and Stable microbiota Is a key indicator of health .

Effect of intestinal flora

Intestinal flora has a significant impact on the treatment response of cancer patients . for example , Patients with leukemia or lymphoma have a high level of... After hematopoietic stem cell transplantation Eubacterium mucosum , The possibility of recurrence or tumor progression is low .

↓↓ Dysbacteriosis of intestinal flora affects anti - PD-L1 Therapeutic effect

human beings 、 Animal and in vitro studies have shown that , Immune regulation of intestinal flora Affect the efficacy of targeted immunotherapy , Such as cytotoxicity T Lymphocyte related 4(CTLA-4) Block and resist PD-L1 Treatment . Consistent with these findings , Some of them are resistant to PD-L1 Patients with epithelial tumors who have been treated with chemotherapy and broad-spectrum antibiotics have experienced treatment failure , The reason may be It leads to the imbalance of the microbiota .

Further supporting these findings is , Fecal transfer from responder and non responder patients to immunocompetent mice leads to mouse antagonism PD-L1 The antibody produced the same response as the corresponding stool transplant donor , So we can prove that Intestinal flora antagonizes PD-L1 The effect of treatment .

↓↓ Intestinal flora regulates the efficacy and toxicity of chemotherapy

Chemotherapy drugs cyclophosphamide and adriamycin can Induce gram positive bacteria ( Lactobacillus yoelii 、 Lactobacillus muris and Enterococcus Heidegger ) Transfer To the secondary lymphoid organs of mice . Once it is transferred to the lymphoid organs , Microbes will stimulate 17 The type and 1 type T The accumulation of helper cell responses , thus Enhance the immune response .

Both preclinical and clinical evidence suggest that , Antibiotics can reduce the effectiveness of chemotherapy . for example , Long term use of antibiotics has been shown to reduce the risk of cyclophosphamide treatment in tumor bearing mice P815 The curative effect of mastocytoma , This supports the importance of bacterial translocation in the gut .

One is right C57BL/6(B6) and 129SvEv(129) Preclinical studies of peripheral neuropathy induced by chemotherapy in mice have shown that , Intestinal bacteria It plays a leading role in determining paclitaxel induced pain sensitivity ; Between sensitive and resistant mice to paclitaxel induced pain , Significant differences in the composition of the intestinal microbiota were observed .

↓↓ Intestinal flora is related to the incidence of gastrointestinal adverse reactions

A clinical study of cervical cancer patients receiving chemotherapy and radiotherapy (n=35) Come to the conclusion , Intestinal microbial diversity and incidence of gastrointestinal toxicity There is a negative correlation .

Again , A study aimed at children with acute lymphocytic leukemia (n=51) Clinical studies have determined , The change of intestinal microbiota during chemotherapy is related to the incidence of gastrointestinal adverse reactions , Such as systemic inflammation and intestinal mucositis .Toll Like receptors (TLRs) Immunomodulatory interactions with gut microbes may Regulate inflammation and healing of colon , To prevent the toxicity of methotrexate chemotherapy .

↓↓ Intestinal flora is fundamentally related to the pathogenesis of mucositis

Mucositis is a common gastrointestinal toxicity , Can cause diarrhea 、 Pain 、 Weight loss and dose limitation . for example , Irinotecan is a known cause Chemotherapy for severe diarrhea . One mechanism of this toxicity may be Some bacteria β- Glucuronidase The role of , These enzymes have been shown to SN-38 It is released into the intestinal cavity to induce diarrhea .

Consistent with this assumption , Through the quinolone antibiotic ciprofloxacin Inhibition of these enzymes can inhibit Irinotecan in the treatment of mice diarrhea , Thus, it is proved that the regulation of intestinal microbiota can Reduce the toxicity of irinotecan .

↓↓ The gut microbiota affects the psychoneurological symptoms associated with cancer treatment

A systematic review evaluated the relationship between the intestinal microbiota and chemotherapy , The conclusion is that , The gut microbiota may affect the psychoneurological symptoms associated with cancer treatment , for example Tired work 、 anxious 、 Depression and sleep disorders .

therefore , Relatively healthy intestinal microbiota can improve the health of cancer patients , Through enhancing the therapeutic effect and reducing the side effects of immunotherapy and chemotherapy, as well as through immune regulation .

Dietary intervention of intestinal flora

Diet affects the composition and diversity of intestinal microbial species . Dietary fiber High intake of dietary fiber is conducive to the increase of bacteria digesting dietary fiber . The mechanism of action is Bacteria that digest dietary fiber produce butyrate And other short chain fatty acids , Nourish intestinal epithelial cells , thus Strengthen intestinal mucosal barrier , enhance Mucosal and systemic immunity .

↓↓  Food supplements Regulating microbiota driven chemotherapeutic toxicity

Due to potential damage to gut barrier and microbiota homeostasis , Chemotherapy is usually associated with changes in the intestinal flora . therefore , Prevention and treatment of chemotherapy-related changes in intestinal flora may Helps prevent chemotherapy related gastrointestinal toxicity .

▸ from Polysaccharides extracted from squid ink After administration of cyclophosphamide in mice Enriched Bifidobacterium , and Reduce Bacteroides , thus Improve intestinal microbiota dysfunction .

▸ Ginseng compounds Sure Enhanced chemotherapy drugs 5- Effect of fluorouracil on colorectal cancer cell line , Especially when these compounds are metabolized by the intestinal microbiota .

▸ Ellagic acid , One common in strawberries 、 Polyphenols in vegetables and fruits such as grapes and blackberries , It is metabolized by intestinal flora to release urolithin , this Yes human beings Colon cancer has antiproliferative properties effect .

↓↓ Prebiotics and probiotics play a role in cancer treatment

Prebiotics （ Indigestible food ingredients that promote the growth of beneficial intestinal microorganisms , Bananas, for example 、 Asparagus and artichokes ） and probiotics （ Microorganisms introduced into the body to play a beneficial role , For example, yogurt 、 Kefir 、 Pickled cabbage resembling sauerkraut 、 Fermented soya bean , And pickles ） It is closely related to the composition of intestinal flora , These substances play a key role in the treatment of cancer .

Many animal and human studies have shown that , Prebiotics 、 Probiotics in Prevent mucositis during chemotherapy Aspect has a powerful role .

For nasopharyngeal carcinoma patients receiving concurrent radiotherapy and chemotherapy , Probiotics combined with radiotherapy , By changing the intestinal flora , appear Enhance host immunity , relieve Related to radiotherapy and chemotherapy Oral mucositis .

VSL #3（ Include Streptococcus thermophiles, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus paracasei, L. delbrueckii subsp. bulgaricus, L. acidophilus, L. plantarum）, During irinotecan treatment , Reduce diarrhea and weight loss in rats .

L. casei, L. rhamnosus, B. bifidum  By inhibiting tumor necrosis factor α、 Interleukin -1b And interleukin -6 mRNA The expression of Reduce chemotherapy-induced diarrhea in mice .

Lactobacillus rhamnosus GG Supplement can Reduce human beings Patients with colorectal cancer stay 5- During fluorouracil chemotherapy Severe diarrhea and abdominal discomfort .

Use Yakult in children receiving chemotherapy Bifidobacterium brevis strain can Prevent fever and reduce the frequency of intravenous antibiotics .

Dietary supplement with prebiotics Fructooligosaccharides and inulin can Zoom in Effects of drugs on mice （5- Fluorouracil 、 Doxorubicin 、 Vincristine 、 Cyclophosphamide 、 Methotrexate 、 Cytarabine ）, So we can prove that Prebiotics and chemotherapy Between Synergy .

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A large number of preclinical data and limited clinical evidence show that , Dietary factors may be preventing and / Or play a role in the treatment of cancer and cancer treatment-related symptoms and toxicity , Data seeking specific dietary interventions are still emerging .

People are also more and more interested in the nature of intestinal flora and its impact on cancer treatment . Look forward to a larger sample size of randomized controlled trials , Further study of dietary interventions .

The best diet is one that the patient is willing and able to follow , Therefore, a certain degree of personalization may be required when introducing these strategies into the clinic .

If we can develop , A drug that improves therapeutic efficacy by regulating intestinal flora , The potential is enormous .

Main references

Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021 Dec 24;374(6575):1632-1640. doi: 10.1126/science.aaz7015. Epub 2021 Dec 23. PMID: 34941392; PMCID: PMC8970537.

Yu ZK, Xie RL, You R, et al. The role of the bacterial microbiome in the treatment of cancer. BMC Cancer. 2021;21(1):934. Published 2021 Aug 19. doi:10.1186/s12885-021-08664-0

Kim AJ, Hong DS, George GC. Dietary influences on symptomatic and non-symptomatic toxicities during cancer treatment: A narrative review. Cancer Treat Rev. 2022 May 13;108:102408. doi: 10.1016/j.ctrv.2022.102408. Epub ahead of print. PMID: 35623220.

Barrea L, Caprio M, Tuccinardi D, Moriconi E, Di Renzo L, Muscogiuri G, Colao A, Savastano S; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group. Could ketogenic diet "starve" cancer? Emerging evidence. Crit Rev Food Sci Nutr. 2022;62(7):1800-1821. doi: 10.1080/10408398.2020.1847030. Epub 2020 Dec 4. PMID: 33274644.

Baguley BJ, Skinner TL, Jenkins DG, Wright ORL. Mediterranean-style dietary pattern improves cancer-related fatigue and quality of life in men with prostate cancer treated with androgen deprivation therapy: A pilot randomised control trial. Clin Nutr. 2021 Jan;40(1):245-254. doi: 10.1016/j.clnu.2020.05.016. Epub 2020 May 25. PMID: 32534948.