Gut microbiota resilience and recovery after anticancer chemotherapy
Abstract
Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a “healthy” gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients’ health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.
Keywords
INTRODUCTION
It is now a fact that the human gut microbiota (GM), i.e., the over trillion microbial cells, mainly bacteria, together with archaea, fungi, and viruses that are hosted in the gastrointestinal tract, plays a multifactorial role in our physiology, from regulation of metabolism to the education and modulation of the immune system, and not least of the nervous system, just to name a few[1,2]. Despite this awareness and the significant advances in the compositional and functional profiling of GM, the precise features of a “healthy” (otherwise called eubiotic) GM are still far from being defined[3]. This is mainly due to the intrinsically plastic nature of GM, which allows it to respond to external perturbations (of limited duration and severity) by oscillating between different stable states associated with health[4]. Indeed, GM differs over time and between individuals, in relation to factors such as diet, lifestyle, environmental exposure, or more generally, what we could define as the exposome[5]. Nonetheless, studies on GM fluctuations in response to these drivers and in comparison with disease settings have made it possible to identify some characteristics shared by eubiotic GMs all over the world, namely a high level of diversity, high relative abundances of bacteria capable of producing beneficial metabolites (mainly short-chain fatty acids - SCFAs, bioactive small molecules with a pluripotent role in human physiology)[6] and low proportions of overt or opportunistic pathogens[7-12]. These features are in fact associated with a healthy gut whose epithelial barrier is intact and whose immune system is adequately trained. In particular, diversity predominantly contributes to the stability of microbial communities, as it allows buffering invasions and facilitates efficient use of resources and, in general, a certain level of functional redundancy, thus supporting the ability to recover rapidly and fully from perturbations, i.e., resilience[4].
However, under certain conditions, the factors listed above, depending on their duration and intensity, can seriously compromise the stability of the GM, pushing it towards an unstable state that, once the perturbation has ceased, can recover to its original state or stabilize in a new alternative, healthy or vice versa dysbiotic (or disease-associated) state[4,13]. More precisely, the GM response to perturbations can be of 3 types: resilience, resistance, or hysteresis. As anticipated above, resilience is the property of a microbial ecosystem that defines how quickly and to what extent it will recover its initial taxonomical and/or functional composition following perturbations[14]. The GM is defined as resistant when it remains substantially unchanged in the face of perturbations. Finally, when the GM fails to recover from disturbance-induced changes and reaches a new stable state, which can be healthy or unhealthy[4], this is called hysteresis[15]. For example, the GM is generally resilient to acute travel-related perturbations [such as dietary changes, contamination of ingested food or water, and possible drug intake (e.g., malaria prophylaxis)], as upon returning home, it tends to recover its original state rather quickly[15,16]. Conversely, antibiotic exposure can dramatically perturb GM, in a manner strongly dependent on the initial state, with potentially long-lasting effects[4,17,18]. In particular, vancomycin use has been associated with a depletion of the relative abundance of beneficial butyrate-producing taxa, such as Coprococcus eutactus and Faecalibacterium prausnitzii, along with a decrease in plasma butyrate concentration, which persisted at 2-month follow-up[18]. Moreover, bacterial species such as Bacteroides thetaiotaomicron and Bifidobacterium adolescentis have recently been shown to be associated with ecological recovery after antibiotic therapy, as they were able to support (and boost) the repopulation of other gut species through specific carbohydrate-degradation and energy-production pathways[19].
In addition to antibiotics, anticancer chemotherapy can be considered another major nuisance for GM. Chemotherapeutic agents can, in fact, have direct effects on the composition of GM as well as destroying gut homeostasis, compromising the integrity of the mucosal barriers and allowing the translocation of microorganisms into the lamina propria and potentially throughout the body, with induction of a strong inflammatory state[20,21]. Depending once again on the initial layout and the specific dynamics that are established during treatment, the GM can favor the therapeutic response or vice versa, the onset of adverse events, including death[22-24]. However, what exactly are the GM signatures associated with a favorable prognosis, a proper recovery process and the underlying driving forces are not yet fully understood. Understanding these aspects may provide valuable opportunities to rationally design microbiome-based intervention strategies aimed at strengthening GM resistance or promoting its ecological recovery, increasing the resilience of healthy states or overcoming that of unhealthy states.
In this narrative review, we focus on anticancer chemotherapy as one of the most profound and impactful ailments for GM. We discuss post-treatment recovery and non-recovery processes of GM in the context of different cancers, paying attention to the main factors influencing these dynamics. Finally, we summarize the current evidence on microbiome-based intervention strategies aimed at supporting rapid and full restocking of a eubiotic GM [Figure 1].
Figure 1. Gut microbiota recovery after chemotherapy treatment. High-impact pharmacological treatments such as chemotherapy can cause profound disturbance of the intestinal environment, including inflammation, breakdown of mucosal barriers, and shifts in the gut microbiota composition. Depending on the initial microbiota state and other treatment-related factors, this perturbation may lead to the establishment of a stable state of “recovery” or “non-recovery”. The recovery state is generally characterized by greater resilience due to greater microbiota diversity and the presence of founders or keystone taxa (e.g., Bacteroides thetaiotaomicron, Bacteroides fragilis, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii), able to favor the repopulation of other commensals, for rapid restoration of a properly functioning eubiotic ecosystem. The non-recovery state is featured by dysbiotic traits such as lower gut microbiota diversity, increased proportions of pathobionts (e.g., Clostridioides difficile, Enterococcus, Staphylococcus, and Escherichia coli), whose colonization and expansion may be promoted by the loss of competing beneficial commensals in an inflammatory environment, and a disrupted intestinal epithelium. Microbiome-targeted interventional strategies (e.g., prebiotics, probiotics, and fecal microbiota transplantation) may facilitate the transition from a non-recovery to a recovery state, thus accelerating the re-establishment of a healthy gut microbiota layout and protecting against the long-term consequences of chemotherapy. The figure was partly generated using Servier Medical Art provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license, and images from Flaticon resources. GM: gut microbiota.
CHEMOTHERAPY-INDUCED ALTERATIONS IN THE GM AND POTENTIAL SIGNATURES OF RECOVERY
In recent years, GM and its metabolites have received a crescendo of attention for their involvement in cancer initiation and progression, as well as in anticancer therapy outcomes[25]. In particular, to date, it is known that there is a bidirectional relationship between GM and anticancer chemotherapy, with the former influencing the efficacy of the treatments, by modulating the immune system and impacting drug pharmacokinetics, and the latter seriously undermining the microbiota stability with potentially long-term consequences for health[26]. Such chemotherapy-related effects on GM can be direct or indirect, i.e., mediated through high-impact side effects, including gastrointestinal toxicity, malnutrition, myelosuppression, hepatoxicity, and neurological symptoms. Indeed, the most common side effects of chemotherapy are abdominal pain, abdominal bleeding, nausea, infections, and diarrhea which are experienced by nearly 80% of oncological patients during treatments. Underlying causes include destruction of the gastrointestinal tract mucosal barrier, with possible onset of mucositis (i.e., inflammation of the mucosa), epithelial cell death, and malabsorption, which fuel (and are fuelled by) the disruption of the GM ecosystem[27]. In fact, chemotherapy acts as a strong stressor on the GM, pushing it towards an unstable and transient state, after which it may or may not recover its initial state (i.e., show or not resilience). As anticipated above, chemotherapy-related perturbations can also lead to a new stable state of health or malaise (so-called hysteresis), which could further favor disease development. How the GM responds to chemotherapy is the result of a complex and multifactorial process that depends on many variables, not just those related to the chemotherapy regimen (i.e., type and dosage of anticancer drugs), but also the type of cancer, the stage of the disease, the co-administration of other drugs, other patient data (demographic, anthropometric, biochemical, genetic, immunological, dietary, etc.), and, of course, the baseline GM configuration. In particular, patients undergoing chemotherapy usually have significantly reduced oral intake due to the side effects of such aggressive treatment, including those mentioned before, such as enteral mucositis and nausea[28,29]. This deterioration of patients’ nutritional status may exacerbate GM dysbiosis and mucosal injury caused by mucositis, ultimately worsening clinical outcomes[30].
In this scenario, understanding GM fluctuations during anticancer treatments is critical to increase the resilience of healthy states (or surpass that of unhealthy states) for rapid and complete restoration of a eubiotic GM configuration associated with a better prognosis. However, also due to the recent awareness of the relationship between gut microbes and anticancer chemotherapy, relatively few studies are present in the literature (please, see Table 1 for a summary of the studies herein discussed). Nevertheless, chemotherapy undoubtedly leads to a reduction in the diversity of the GM[23,24,31,32], with a consequent potential loss of functional redundancy (although mostly not experimentally verified), which appears crucial for the stability of the GM during perturbations and, therefore, for its resilience. The first studies in this field were conducted on murine models treated with different chemotherapeutics, showing increased levels of Bacteroides[33-36]. However, Bacteroides were also shown to decrease following chemotherapy treatments, along with some beneficial microbes such as Bifidobacterium and Lactobacillus spp.[37-39]. With regard to human studies, Zwielehner et al. analyzed the GM profile of 17 patients with different types of cancer before and after chemotherapy. Pharmacological treatment promoted a slight increase in Bacteroides spp., as well as pathobionts not detected before treatment (e.g., Clostridioides difficile, Enterococcus faecium)[40]. Fei et al. found decreased microbial richness (i.e., the total number of species in a given sample) and diversity (which refers, depending on the metric used, to either richness or evenness, or both, and can also take into account phylogenetic relationships), in colorectal cancer patients receiving antimetabolites and platinum-based chemotherapeutic agents[41], while post-treatment enrichment of Bacteroides was found[42]. An elegant study from Youssef et al.[43] compared the GM profile of patients with untreated gastrointestinal malignancies
Clinical studies investigating gut microbiota variations during chemotherapy treatments
| Study | Cancer type | Treatment | Number of patients | Main results |
| D'Amico et al.[23] | Epithelial ovarian cancer | Surgery + chemotherapy with platinum and taxane compounds | 24 | - Treatment-related decrease in health-promoting SCFA-producing taxa, such as Lachnospiraceae and Ruminococcaeae - Increased levels of Coriobacteriaceae and Bifidobacterium over time were associated with platinum resistance and non-response to therapy |
| Peled et al.[24] | Hematological malignancies | Various intensities of conditioning regimens before HSCT | 1362 | - Reduction in bacterial diversity after treatment - Non-recovers showed an increased risk of infections, aGvHD, and relapse |
| Biagi et al.[31] | Hematological malignancies (pediatric patients) | Conditioning regimens based on busulfan before HSCT | 10 | - Only 10% of pre-existing species resisted after HSCT, with Bacteroides spp. being the most represented among the persistent ones - A decrease in the relative abundance of health-associated taxa, such as Faecalibacterium and Ruminococcus, after HSCT - Pre-HSCT samples of aGvHD patients showed a lower abundance of Parabacteroides and Bacteroides |
| Biagi et al.[32] | Hematological malignancies (pediatric patients) | Conditioning regimens (busulfan, cyclophosphamide/fludarabine, total body irradiation) before HSCT | 36 | - Reduced microbial diversity, lower Blautia content, and increase in Fusobacterium abundance were predictive gut microbiota signatures of subsequent aGvHD occurrence |
| Zwielehner et al.[40] | Various types of malignancies (e.g., urothelial carcinoma, multiple myeloma, non-Hodgkin lymphoma, ovarian fibroma, leukemia, small intestinal tumor, rectal tumor, colon tumor) | Chemotherapy (antimetabolites, alkylating agents, monoclonal antibodies, corticosteroids, plant alkaloids, platinum-containing compounds, radiation therapy, anthracyclines, cytotoxic topoisomerase I and II inhibitors) | 17 | - Decreased species richness after chemotherapy in comparison with healthy individuals - Increase in Bacteroides spp. during chemotherapy - Decreased abundances of Bifidobacterium and Clostridium clusters IV and XIVa after chemotherapy - Enterococcus faecium increased following chemotherapy - The occurrence of Clostridioides difficile in 3/17 subjects was associated with a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella, and the species Faecalibacterium prausnitzii |
| Fei et al.[41] | Stage III colorectal cancer | Chemotherapy (capecitabine + oxaliplatin) | 17 | - Patients with CID, compared with those who did not experience CID, had lower bacterial richness along with increased Proteobacteria, Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae (particularly Klebsiella pneumoniae) - Patients who did not develop CID had increased abundances of Clostridia, Clostridiales, Ruminococcaceae, and Bacteroidetes - In general, an increased abundance of Bacteroidales, Bacteroidaceae, and Bacteroides was observed |
| Deng et al.[42] | CRC patients before any chemotherapy treatments, CRC patients surgically treated, and CRC patients treated with chemotherapy | Chemotherapy (5-FU + oxaliplatin) | 17 (CRC before chemotherapy) 14 (CRC after pharmacological treatment) 5 (CRC surgically treated) | - Surgery affected the structure of the gut microbiota as demonstrated by multivariate analysis based on Bray-Curtis similarity, and decreased biodiversity - Bacteroidetes was the most abundant phylum in healthy controls and CRC patients before and after chemotherapy - Fusobacterium, Oscillospira, and Prevotella were detected in CRC patients before and after chemotherapy - Veillonella dispar, Prevotella copri, and Bacteroides plebeius were only enriched in CRC patients treated with chemotherapy - Proteobacteria phylum was found in high abundance in CRC patients after surgery |
| Youssef et al.[43] | Stomach, pancreas, small intestine, colon, and rectum cancer | Chemotherapy and/or radiotherapy | 20 (treated patients) 43 (non-treated patients) | - Lactobacillaceae and Lactobacillus were observed at higher relative abundances in the treated group compared to the non-treated group |
| Stringer et al.[44] | Various types of cancer (colorectal, breast, laryngeal, esophageal, and melanoma) | Chemotherapy (capecitabine, cisplatin/5-FU, FOLFOX4, FOLFOX6, FOLFIRI, 5-FU/folinic acid, paclitaxel, carboplatin and gemcitabine) | 16 | - Reduced proportions of Lactobacillus spp., Bacteroides spp., Bifidobacterium spp., and Enterococcus spp., and increased proportions of Staphylococcus spp. and Escherichia coli were observed in patients undergoing chemotherapy compared to healthy controls |
| Tong et al.[45] | Ovarian cancer | Surgery and chemotherapy (carboplatin, paclitaxel, cisplatin) | 18 | - The proportions of Bacteroidetes and Firmicutes increased after treatment, while those of Proteobacteria decreased - Anaerobic bacteria, such as Bacteroides, Collinsella, and Blautia, exhibited a significant increase after chemotherapy |
| Galloway-Peña et al.[47] | Acute myeloid leukemia | Induction chemotherapy | 34 | - Loss of bacterial diversity during chemotherapy - Decreased bacterial diversity at baseline was associated with a higher risk of infection - Chemotherapy treatment led to increased abundances of the genus Lactobacillus - The gut microbiota of patients treated with chemotherapy was dominated by a single taxon, most frequently by opportunistic pathogens (e.g., Staphylococcus, Enterobacter, and Escherichia) |
| Han et al.[51] | Acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome | Myeloablative regimens (busulfan + cyclophosphamide and total body irradiation + cyclophosphamide) then sequential intensified regimen (fludarabine + cytarabine + total body irradiation + cyclophosphamide + etoposide) | 141 | - Proteobacteria, Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae were associated with aGvHD - Lower microbiota diversity in the aGvHD group compared with the non-aGvHD group - The gut microbiota and conditioning might induce aGvHD by influencing the T regulatory/T helper 17 cell balance |
| Montassier et al.[52] | Non-Hodgkin’s lymphoma | Myeloablative conditioning regimen (high dose carmustine, etoposide, aracytine, and melphalan) | 28 | - Chemotherapy-related decrease in Firmicutes and Actinobacteria and increase in Proteobacteria |
| Montassier et al.[53] | Non-Hodgkin’s lymphoma | Myeloablative conditioning regimen (high dose carmustine, etoposide, aracytine, and melphalan) | 8 | - Bacterial diversity decreased after chemotherapy - Drastic decrease in Firmicutes (in particular, Faecalibacterium, Blautia, and Roseburia) and Bifidobacterium after treatment - The relative abundance of Bacteroides increased during chemotherapy, as well as that of Proteobacteria - A shift from Gram-positive to Gram-negative bacteria was observed |
| Rashidi et al.[54] | Acute myeloid leukemia | Chemotherapy | 52 | - Higher relative abundances of Bacteroides and lower amounts of Faecalibacterium and Alistipes were detected up to 6 months after chemotherapy |
| Rajagopala et al.[55] | Acute lymphoblastic leukemia in pediatric patients | Chemotherapy | 32 | - Microbiota diversity and richness were significantly lower at diagnosis and during chemotherapy in comparison with healthy controls - The abundance of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen - At diagnosis, higher proportions of Bacteroidetes (particularly Bacteroides) and lower proportions of Faecalibacterium were found in patients compared with healthy controls - Alistipes proportions decreased substantially during chemotherapy, while Lachnospiraceae increased during treatment |
In parallel, some research has focused on the GM recovery processes in adult and pediatric patients affected by hematologic malignancies undergoing hematopoietic stem cell transplantations (HSCT). HSCT can lead to several life-threatening complications, such as graft-versus-host disease (GvHD, i.e., when alloreactive donor T cells attack host organs, such as skin, liver, and gut), and local and systemic infections. In this context, several studies showed that treatment-related GM unbalances are associated with poor clinical outcomes[48]. Indeed, HSCT practices significantly affect GM homeostasis with a reduction in the diversity and sometimes monodominance by Proteobacteria, Enterococcus, or Streptococcus[31,32,49-53]. Notably, chemotherapy treatments in adult patients have been found to trigger a lasting shift in the GM, with higher relative abundances of Bacteroides and lower proportions of Faecalibacterium and Alistipes detected up to 6 months of follow-up[54]. Similar results were confirmed in pediatric patients with various hematological malignancies who underwent HSCT[31,32]. Their GM profile was analyzed before and up to 4 months after HSCT, showing the presence of severe dysbiosis, as well as the invasion of newly acquired bacterial species. According to the authors, only 10% of pre-existing species resisted after HSCT, with Bacteroides spp. being the most represented among the persistent ones. Also, a decrease in the relative abundance of health-associated taxa, such as Faecalibacterium and Ruminococcus, was found after HSCT. In general, patients who did recover a healthy GM configuration after HSCT showed a better prognosis, while non-recoverers showed an increased risk of infections, aGvHD, and relapse[24,32]. Conflicting results have also been reported regarding the timing of GM recovery, i.e., return to a layout similar to the pre-treatment one. Some studies reported that total bacterial abundance was restored in a few days[40], while in others, a more persistent shift was found, and the GM recovered its initial richness and metabolic capability several months after treatment[31,54,55]. These differences in the speed and extent of recovery could be explained by GM layouts before treatment. For example, studies carried out in different contexts have consistently shown that a high-diversity GM is more stable and resilient to perturbations[56-58].
Again, Bacteroides was identified as a key player, potentially capable of fostering the re-establishment of the microbial community. In fact, it was preserved during anticancer treatments, resisting not only the perturbations of chemotherapy but also those of antimicrobial therapy. Regarding this last point, a brilliant study by Chng et al.[19] found 21 bacterial species with robust associations with post-antibiotic therapy recovery, in particular belonging to the Bacteroides genus - i.e., B. uniformis, B. thetaiotaomicron, B. stercoris, B. egghertii, B. coprocola, B. caccae, and B. intestinalis. The reason for the persistence of Bacteroides during and after treatments may lie in its ability to penetrate the colonic mucus layer and reside within the crypt channels, a region that is more protected and less susceptible to stressors[59,60]. Not surprisingly, Bacteroides fragilis mutants for carbohydrate utilization systems that are unable to colonize the mucus layer are also less resistant to intestinal perturbations, such as antibiotic treatments and pathogen infections[60]. As suggested elsewhere, the breakdown of mucins and complex polysaccharides[61] could be one of the functions that allow members of the Bacteroidetes phylum to stabilize the GM community[62], thus acting as “primary gut species” after perturbations, which contribute to microbiota repopulation[19,63].
INTERVENTION STRATEGIES TO PROMOTE THE RECOVERY OF GM AFTER CHEMOTHERAPY
Nowadays, GM has effectively become a target of clinical practice in cancer management[64,65]. Its close relationship with host well-being has paved the way for the development of precision personalized intervention strategies aimed at promoting more resilient healthy GM configurations associated with a better prognosis[22,66,67]. Here, we briefly discuss the potential of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as GM manipulation tools to promote its recovery after chemotherapy treatment[66,68,69].
Prebiotics are defined as “a substrate that is selectively utilized by host microorganisms conferring a health benefit”[70]. Most of the prebiotics currently used are based on carbohydrates such as inulin, fructo-oligosaccharides, galacto-oligosaccharides, lactulose, and human milk oligosaccharides[68,71-73]. However, other substances, such as polyphenols[74] and polyunsaturated fatty acids[75], are being studied for their beneficial effects on host health. These compounds pass through digestion in the small intestine, reaching the colon virtually unaffected, where they can be fermented by numerous bacterial taxa into SCFAs[76]. Although the information on the use of prebiotics in cancer patients is currently limited, they undoubtedly represent a means of promoting GM resistance and resilience[77]. In particular, their metabolism is known to involve the establishment of syntrophic cross-feeding interactions[77,78,79], which are essential for the ecological health of GM, and could therefore favor the persistence and/or repopulation of beneficial commensals for more rapid restoration of microbial diversity and abundance.
Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”[80]. Probiotic intake can restore the GM composition and its health-associated functions, limiting pathogens or unhealthy microbial expansions[81,82]. The underlying mechanisms include competition for receptor and binding sites, promotion of intestinal mucosa integrity, and production of a range of molecules, including antimicrobial agents, to name a few[82-84]. Again, there is little information on the potential of probiotics to specifically promote GM recovery after chemotherapy, but several trials have explored their efficacy in improving clinical outcomes[21,65]. Notably, a recent randomized, double-blind, placebo-controlled trial reported that oral administration of a mixture of six viable probiotic strains of lactobacilli and bifidobacteria reduced levels of pro-inflammatory cytokines (i.e., TNF-α, IL-17A, IL-17C, IL-22, and IL-12), but also of IL-10, and prevented post-surgical complications in patients with colorectal cancer (NCT03782428)[85]. It should be noted that, although generally considered an anti-inflammatory cytokine, IL-10 has been shown to play a dual role in immunology, as well as tumor pathogenesis and/or progression, with increased levels associated with colorectal cancer progression and poor patient survival[86-88]. In addition, a phase II randomized clinical trial showed that an oral probiotic cocktail (containing Lactobacillus plantarum MH-301, Bifidobacterium animalis subsp. lactis LPL-RH, Lactobacillus rhamnosus LGG-18, and Lactobacillus acidophilus) could alleviate the severity of oral mucositis in patients with nasopharyngeal cancer treated with radiotherapy and chemotherapy by regulating GM dysbiosis and enhancing immune system response (NCT03112837)[89]. However, as discussed above, the role of probiotics, especially Bifidobacterium spp., may not be entirely favorable during chemotherapy treatments, making the conduct of further clinical studies extremely important. In particular, future studies should investigate the effects of the early intake of probiotics as “GM pre-conditioning” on chemotherapy outcomes and the occurrence of side effects. Administration of the traditional probiotic E. coli Nissle 1917 could also be a promising approach for colorectal cancer control, possibly due to its pro-apoptotic effect through upregulation of PTEN (phosphatase and tensin homolog) and Bax and downregulation of AKT1[90]. However, with specific regard to GM resilience, it should be noted that the choice of probiotics to be administered should be rationally guided by the knowledge of which are the keystone species associated with GM recovery, which most likely do not include lactobacilli and bifidobacteria (generally subdominant taxa if not absent in adult GMs) but the so-called next-generation probiotics or live biotherapeutics[91]. For example, some Bacteroides species, such as B. fragilis and B. thetaiotaomicron, have shown intriguing therapeutic effects on immune derangement and intestinal epithelial barrier impairment, possibly favoring a healthy repopulation of the gut[19,92-95]. Additionally, Bacteroides xylanisolvens DSM 23964 has been tested in a phase I clinical trial. Heat-inactivated preparations of this organism are hypothesized to improve therapeutic response and cancer immune surveillance by increasing Thomsen-Friedenreich α-specific IgM[96], but the impact on GM recovery is currently unknown.
FMT consists of the transfer of healthy donor stools into the gastrointestinal tract of a patient to improve the dysbiotic state by increasing the overall diversity and restoring the functionality of the GM[97]. FMT is currently used for the treatment of recurrent C. difficile infection[98] when antibiotics (e.g., vancomycin) and monoclonal antibodies (e.g., bezlotoxumab) fail, as suggested by international guidelines[99,100]. In this context, its efficacy rate is between 80% and 90%, as reported by several meta-analyses and randomized clinical trials[101-104]. However, some concerns regarding the long-term safety of FMT are emerging, particularly the risk of transfer of pathogens and antibiotic-resistant genes from donor to recipient and/or the occurrence of autoimmunological disorders, which makes the choice of an appropriate donor of utmost importance[105,106]. Furthermore, another important issue concerns the viability of anaerobic microbes, of which GM is largely composed. For example, Papanicolas et al.[107] found that the practice of preparing material for FMT in ambient air profoundly affected the microbial viability, disproportionally reducing the abundance of anaerobic commensals (including the health-associated taxa F. prausnitzii and Eubacterium hallii) and the biosynthetic capacity of important anti-inflammatory metabolites. As regards anticancer chemotherapy, as expected, exhaustive information on the application of FMT is not yet available, but some clinical trials have been completed and others are still ongoing. For example, in the single-arm phase II multicenter study by Malard et al. (NCT02928523)[108], 25 patients with acute myeloid leukemia were successfully treated with autologous FMT to restore GM dysbiosis and increase biodiversity. In particular, FMT facilitated the restoration of high proportions of health-associated taxa, such as Lachnospiraceae, Ruminococcaceae, and other Clostridiales (generally dominant in the adult GM), while the decrease of pro-inflammatory taxa belonging to the Enterobacteriaceae and Enterococcaceae families, which instead predominated during chemotherapy potentially undermining GM recovery.
CONCLUSION
In the present review, we discussed the available literature on GM dynamics during anticancer chemotherapy, one of the most detrimental stressors to which the human body and its microbial counterpart can be exposed. While the devastating impact of chemotherapy on GM is well established, especially in terms of biodiversity reduction and loss of health-associated taxa, with potential expansion of pathobionts, the theme of GM resilience and recovery has not yet been sufficiently explored. Indeed, most of the available evidence concerns the ability of only one GM genus, Bacteroides, to withstand environmental stresses and help rebuild the microbial community. Although GM dynamics in a context such as cancer may seem at first glance to be of little relevance, identifying taxa associated with ecological recovery and understanding their interactions for a rapid, complete, and healthy community restocking would be of paramount importance as it could guide the rational design of microbiome-based adjuvant strategies to promote response to therapy and limit long-term negative consequences for oncological patients’ health. In this regard, GM manipulation tools such as prebiotics, probiotics, and FMT have shown promising results, but again, no particular attention has been paid to whether and to what extent and how quickly they allow the recovery of a eubiotic GM. Future studies should unravel such aspects for a revolution in the clinical approach, which places the evidence and the mechanisms of action as the basis of the choice of intervention strategies.
DECLARATIONS
Authors’ contributionsWrote the original draft: Roggiani S, Mengoli M, Conti G, Fabbrini M
Reviewed and edited the manuscript: Turroni S, D'Amico F, Barone M
Supervised during the draft preparation: Brigidi P, Turroni S
All authors have read and agreed to the published version of the manuscript.
Availability of data and materialsNot applicable.
Financial support and sponsorshipNone.
Conflicts of interestAll authors declared that there are no conflicts of interest.
Ethical approval and consent to participateNot applicable.
Consent for publicationNot applicable.
Copyright© The Author(s) 2023.
REFERENCES
1. DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 2016;22:1137-50.
2. Barone M, D'Amico F, Fabbrini M, Rampelli S, Brigidi P, Turroni S. Over-feeding the gut microbiome: a scoping review on health implications and therapeutic perspectives. World J Gastroenterol 2021;27:7041-64.
3. Shanahan F, Ghosh TS, O'Toole PW. The healthy microbiome-what is the definition of a healthy gut microbiome? Gastroenterology 2021;160:483-94.
4. Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut 2021;70:595-605.
5. Wild CP. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev 2005;14:1847-50.
6. Turroni S, Brigidi P, Cavalli A, Candela M. Microbiota-host transgenomic metabolism, bioactive molecules from the inside. J Med Chem 2018;61:47-61.
8. Duvallet C, Gibbons SM, Gurry T, Irizarry RA, Alm EJ. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat Commun 2017;8:1784.
9. Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med 2017;15:73.
10. Almeida A, Mitchell AL, Boland M, et al. A new genomic blueprint of the human gut microbiota. Nature 2019;568:499-504.
11. Nayfach S, Shi ZJ, Seshadri R, Pollard KS, Kyrpides NC. New insights from uncultivated genomes of the global human gut microbiome. Nature 2019;568:505-10.
12. Pasolli E, Asnicar F, Manara S, et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell 2019;176:649-662.e20.
13. Relman DA. The human microbiome: ecosystem resilience and health. Nutr Rev 2012;70 Suppl 1:S2-9.
14. Sommer F, Anderson JM, Bharti R, Raes J, Rosenstiel P. The resilience of the intestinal microbiota influences health and disease. Nat Rev Microbiol 2017;15:630-8.
15. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature 2012;489:220-30.
16. Kampmann C, Dicksved J, Engstrand L, Rautelin H. Changes to human faecal microbiota after international travel. Travel Med Infect Dis 2021;44:102199.
17. Hildebrand F, Moitinho-Silva L, Blasche S, et al. Antibiotics-induced monodominance of a novel gut bacterial order. Gut 2019;68:1781-90.
18. Reijnders D, Goossens GH, Hermes GD, et al. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: a randomized double-blind placebo-controlled trial. Cell Metab 2016;24:63-74.
19. Chng KR, Ghosh TS, Tan YH, et al. Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut. Nat Ecol Evol 2020;4:1256-67.
20. Roy S, Trinchieri G. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer 2017;17:271-85.
21. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018;359:97-103.
22. D'Amico F, Barone M, Tavella T, Rampelli S, Brigidi P, Turroni S. Host microbiomes in tumor precision medicine: how far are we? Curr Med Chem 2022;29:3202-30.
23. D'Amico F, Perrone AM, Rampelli S, et al. Gut microbiota dynamics during chemotherapy in epithelial ovarian cancer patients are related to therapeutic outcome. Cancers 2021;13:3999.
24. Peled JU, Gomes ALC, Devlin SM, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med 2020;382:822-34.
25. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med 2016;375:2369-79.
26. Conti G, D'Amico F, Fabbrini M, Brigidi P, Barone M, Turroni S. Pharmacomicrobiomics in anticancer therapies: why the gut microbiota should be pointed out. Genes 2022;14:55.
27. Secombe KR, Coller JK, Gibson RJ, Wardill HR, Bowen JM. The bidirectional interaction of the gut microbiome and the innate immune system: implications for chemotherapy-induced gastrointestinal toxicity. Int J Cancer 2019;144:2365-76.
28. Green R, Horn H, Erickson JM. Eating experiences of children and adolescents with chemotherapy-related nausea and mucositis. J Pediatr Oncol Nurs 2010;27:209-16.
29. Ottosson S, Laurell G, Olsson C. The experience of food, eating and meals following radiotherapy for head and neck cancer: a qualitative study. J Clin Nurs 2013;22:1034-43.
30. Costa RGF, Caro PL, de Matos-Neto EM, et al. Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa. J Cachexia Sarcopenia Muscle 2019;10:1116-27.
31. Biagi E, Zama D, Nastasi C, et al. Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT. Bone Marrow Transplant 2015;50:992-8.
32. Biagi E, Zama D, Rampelli S, et al. Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. BMC Med Genomics 2019;12:49.
33. Fijlstra M, Ferdous M, Koning AM, Rings EH, Harmsen HJ, Tissing WJ. Substantial decreases in the number and diversity of microbiota during chemotherapy-induced gastrointestinal mucositis in a rat model. Support Care Cancer 2015;23:1513-22.
34. Stojanovska V, McQuade RM, Fraser S, et al. Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. PLoS One 2018;13:e0198359.
35. Wu J, Gan Y, Li M, et al. Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota. Biomed Pharmacother 2020;124:109883.
36. Yuan W, Xiao X, Yu X, et al. Probiotic therapy (BIO-THREE) mitigates intestinal microbial imbalance and intestinal damage caused by oxaliplatin. Probiotics Antimicrob Proteins 2022;14:60-71.
37. Forsgård RA, Marrachelli VG, Korpela K, et al. Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats. Cancer Chemother Pharmacol 2017;80:317-32.
38. Xu X, Zhang X. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiol Res 2015;171:97-106.
39. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Keefe DM. Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol Ther 2008;7:1919-25.
40. Zwielehner J, Lassl C, Hippe B, et al. Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR, 454 sequencing and PCR-DGGE fingerprinting. PLoS One 2011;6:e28654.
41. Fei Z, Lijuan Y, Xi Y, et al. Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer. Gut Pathog 2019;11:18.
42. Deng X, Li Z, Li G, Li B, Jin X, Lyu G. Comparison of microbiota in patients treated by surgery or chemotherapy by 16S rRNA sequencing reveals potential biomarkers for colorectal cancer therapy. Front Microbiol 2018;9:1607.
43. Youssef O, Lahti L, Kokkola A, et al. Stool microbiota composition differs in patients with stomach, colon, and rectal neoplasms. Dig Dis Sci 2018;63:2950-8.
44. Stringer AM, Al-Dasooqi N, Bowen JM, et al. Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases. Support Care Cancer 2013;21:1843-52.
45. Tong J, Zhang X, Fan Y, et al. Changes of intestinal microbiota in ovarian cancer patients treated with surgery and chemotherapy. Cancer Manag Res 2020;12:8125-35.
46. Huang B, Gui M, Ni Z, et al. Chemotherapeutic drugs induce different gut microbiota disorder pattern and NOD/RIP2/NF-κB signaling pathway activation that lead to different degrees of intestinal injury. Microbiol Spectr 2022;10:e0167722.
47. Galloway-Peña JR, Smith DP, Sahasrabhojane P, et al. The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia. Cancer 2016;122:2186-96.
48. Zeiser R, Blazar BR. Acute graft-versus-host disease - biologic process, prevention, and therapy. N Engl J Med 2017;377:2167-79.
49. Jenq RR, Ubeda C, Taur Y, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 2012;209:903-11.
50. Eriguchi Y, Takashima S, Oka H, et al. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins. Blood 2012;120:223-31.
51. Han L, Zhang H, Chen S, et al. Intestinal microbiota can predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2019;25:1944-55.
52. Montassier E, Gastinne T, Vangay P, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther 2015;42:515-28.
53. Montassier E, Batard E, Massart S, et al. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation. Microb Ecol 2014;67:690-9.
54. Rashidi A, Ebadi M, Rehman TU, et al. Lasting shift in the gut microbiota in patients with acute myeloid leukemia. Blood Adv 2022;6:3451-7.
55. Rajagopala SV, Singh H, Yu Y, et al. Persistent gut microbial dysbiosis in children with acute lymphoblastic leukemia (ALL) during chemotherapy. Microb Ecol 2020;79:1034-43.
56. Kootte RS, Levin E, Salojärvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab 2017;26:611-619.e6.
57. Salonen A, Lahti L, Salojärvi J, et al. Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J 2014;8:2218-30.
58. Tap J, Furet JP, Bensaada M, et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ Microbiol 2015;17:4954-64.
59. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 2016;14:20-32.
60. Lee SM, Donaldson GP, Mikulski Z, Boyajian S, Ley K, Mazmanian SK. Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 2013;501:426-9.
62. Trosvik P, de Muinck EJ. Ecology of bacteria in the human gastrointestinal tract--identification of keystone and foundation taxa. Microbiome 2015;3:44.
64. D'Amico F, Decembrino N, Muratore E, et al. Oral lactoferrin supplementation during induction chemotherapy promotes gut microbiome eubiosis in pediatric patients with hematologic malignancies. Pharmaceutics 2022;14:1705.
65. Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med 2019;25:377-88.
66. Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene 2020;39:4925-43.
67. Javdan B, Lopez JG, Chankhamjon P, et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 2020;181:1661-1679.e22.
68. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol 2019;16:605-16.
69. Ting NL, Lau HC, Yu J. Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes. Gut 2022;71:1412-25.
70. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 2017;14:491-502.
71. Messaoudene M, Pidgeon R, Richard C, et al. A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota. Cancer Discov 2022;12:1070-87.
72. García-Peris P, Velasco C, Lozano MA, et al. Effect of a mixture of inulin and fructo-oligosaccharide on Lactobacillus and Bifidobacterium intestinal microbiota of patients receiving radiotherapy: a randomised, double-blind, placebo-controlled trial. Nutr Hosp 2012;27:1908-15.
73. Wang Y, Li H. Gut microbiota modulation: a tool for the management of colorectal cancer. J Transl Med 2022;20:178.
74. Fabbrini M, D'Amico F, Barone M, et al. Polyphenol and tannin nutraceuticals and their metabolites: how the human gut microbiota influences their properties. Biomolecules 2022;12:875.
75. Rinninella E, Costantini L. Polyunsaturated fatty acids as prebiotics: innovation or confirmation? Foods 2022;11:146.
76. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes 2017;8:172-84.
77. Guarino MPL, Altomare A, Emerenziani S, et al. Mechanisms of action of prebiotics and their effects on gastro-intestinal disorders in adults. Nutrients 2020;12:1037.
78. Jean-Pierre F, Henson MA, O'Toole GA. Metabolic modeling to interrogate microbial disease: a tale for experimentalists. Front Mol Biosci 2021;8:634479.
79. Klünemann M, Andrejev S, Blasche S, et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature 2021;597:533-8.
80. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506-14.
81. Wieërs G, Belkhir L, Enaud R, et al. How probiotics affect the microbiota. Front Cell Infect Microbiol 2019;9:454.
82. Zyl WF, Deane SM, Dicks LMT. Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria. Gut Microbes 2020;12:1831339.
83. Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of action of probiotics. Adv Nutr 2019;10:S49-66.
84. Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med 2019;25:716-29.
85. Zaharuddin L, Mokhtar NM, Muhammad Nawawi KN, Raja Ali RA. A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer. BMC Gastroenterol 2019;19:131.
86. Mannino MH, Zhu Z, Xiao H, Bai Q, Wakefield MR, Fang Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett 2015;367:103-7.
87. Stanilov N, Deliysky T, Jovchev J, Stanilova S. Advanced colorectal cancer is associated with enhanced Il-23 and IL-10 serum levels. Lab Med 2010;41:159-63.
88. Miteva LD, Stanilov NS, Deliysky TS, Stanilova SA. Significance of -1082A/G polymorphism of IL10 gene for progression of colorectal cancer and IL-10 expression. Tumour Biol 2014;35:12655-64.
89. Xia C, Jiang C, Li W, et al. A phase II randomized clinical trial and mechanistic studies using improved probiotics to prevent oral mucositis induced by concurrent radiotherapy and chemotherapy in nasopharyngeal carcinoma. Front Immunol 2021;12:618150.
90. Alizadeh S, Esmaeili A, Omidi Y. Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways. Iran J Basic Med Sci 2020;23:886-93.
91. O'Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat Microbiol 2017;2:17057.
92. Zhou Q, Shen B, Huang R, et al. Bacteroides fragilis strain ZY-312 promotes intestinal barrier integrity via upregulating the STAT3 pathway in a radiation-induced intestinal injury mouse model. Front Nutr 2022;9:1063699.
93. Deng H, Li Z, Tan Y, et al. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages. Sci Rep 2016;6:29401.
94. Liu Q, Yu Z, Tian F, et al. Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microb Cell Fact 2020;19:1-11.
95. Sofi MH, Wu Y, Ticer T, et al. A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD. JCI Insight 2021;6:136841.
96. Ulsemer P, Toutounian K, Schmidt J, Karsten U, Goletz S. Preliminary safety evaluation of a new Bacteroides xylanisolvens isolate. Appl Environ Microbiol 2012;78:528-35.
97. Allegretti JR, Mullish BH, Kelly C, Fischer M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet 2019;394:420-31.
98. Mengoli M, Barone M, Fabbrini M, D'Amico F, Brigidi P, Turroni S. Make it less difficile: understanding genetic evolution and global spread of clostridioides difficile. Genes 2022;13:2200.
99. Chaar A, Feuerstadt P. Evolution of clinical guidelines for antimicrobial management of Clostridioides difficile infection. Therap Adv Gastroenterol 2021;14:17562848211011953.
100. Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the infectious diseases society of America (IDSA) and society for healthcare epidemiology of America (SHEA): 2021 focused update guidelines on management of clostridioides difficile infection in adults. Clin Infect Dis 2021;73:e1029-44.
101. Ianiro G, Maida M, Burisch J, et al. Efficacy of different faecal microbiota transplantation protocols for Clostridium difficile infection: a systematic review and meta-analysis. United European Gastroenterol J 2018;6:1232-44.
102. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-15.
103. Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: “RePOOPulating” the gut. Microbiome 2013;1:3.
104. Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther 2017;46:479-93.
105. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017;66:569-80.
106. Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut 2018;67:1920-41.
107. Papanicolas LE, Choo JM, Wang Y, et al. Bacterial viability in faecal transplants: which bacteria survive? EBioMedicine 2019;41:509-16.
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Roggiani S, Mengoli M, Conti G, Fabbrini M, Brigidi P, Barone M, D'Amico F, Turroni S. Gut microbiota resilience and recovery after anticancer chemotherapy. Microbiome Res Rep 2023;2:16. http://dx.doi.org/10.20517/mrr.2022.23
AMA Style
Roggiani S, Mengoli M, Conti G, Fabbrini M, Brigidi P, Barone M, D'Amico F, Turroni S. Gut microbiota resilience and recovery after anticancer chemotherapy. Microbiome Research Reports. 2023; 2(3): 16. http://dx.doi.org/10.20517/mrr.2022.23
Chicago/Turabian Style
Roggiani, Sara, Mariachiara Mengoli, Gabriele Conti, Marco Fabbrini, Patrizia Brigidi, Monica Barone, Federica D'Amico, Silvia Turroni. 2023. "Gut microbiota resilience and recovery after anticancer chemotherapy" Microbiome Research Reports. 2, no.3: 16. http://dx.doi.org/10.20517/mrr.2022.23
ACS Style
Roggiani, S.; Mengoli M.; Conti G.; Fabbrini M.; Brigidi P.; Barone M.; D'Amico F.; Turroni S. Gut microbiota resilience and recovery after anticancer chemotherapy. Microbiome. Res. Rep. 2023, 2, 16. http://dx.doi.org/10.20517/mrr.2022.23
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