Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 926 - файл
.pdf
316 N. R. Suss and B. D. Shogan
https://t.me/med1917
12.5.2 Inflammatory Bowel Disease
IBD is believed to result from the complex interaction between the intestinal
microbiome and the host immune system [58]. While the exact mechanism by
which intestinal dysbiosis contributes to IBD development remains to be elucidated, there is reason to believe that microbial manipulation and restoration
through FMT may have a critical role in disease management. Paramsothy et al.
conducted a multicenter, double-blinded, randomized controlled trial in which
patients with active ulcerative colitis were randomized to either FMT (n = 41)
or placebo (n = 40) enemas 5 days per week for 8 weeks with a primary outcome measure of steroid-free clinical remission with endoscopic remission or
response [59]. At week 8, 11 (27%) of 41 patients treated with FMT and 3 (8%)
of 40 patients who received the placebo enemas demonstrated clinical and endoscopic evidence of disease remission. In FMT-treated patients 44% demonstrated
steroid-free clinical remission at the end of week 8, compared to only 20% of
placebo-treated patients; 54% of FMT-treated patients achieved a steroid-free clinical response compared to just 23% of placebo-treated patients. Lastly, they found
that steroid-free endoscopic response measured by the Mayo score was appreciated in 32% of patients assigned FMT compared to 10% of those assigned to
the placebo group. Treatment or protocol failure occurred in 22% of patients in
the FMT group and 28% in the placebo group due to worsening of symptoms
with steroid taper, symptom persistence or worsening in the absence of steroid
taper, and non-compliance. Faecal stool sample analysis demonstrated that operational taxonomic units and phylogenetic diversity increased significantly compared
to baseline samples in patients assigned to FMT; these findings were present at
4 weeks, 8 weeks, and persisted beyond 8 weeks. Patients who underwent FMT
saw a shift in their gut microbial profiles from a dominance of Bacteroides spp to
Prevotella. On a taxonomic level, Barnesiella spp, Parabacteroides spp, Clostrid-
ium cluster IV, and Ruminococcus spp were associated with remission after FMT,
whereas Fusobacterium spp and Sutterella spp were associated with no remission after FMT. This finding is particularly interesting, as Fusobacterium has been
associated with UC pathogenesis in previous studies [59]. Based on these findings, the authors concluded that there exists a subset of patients with active UC
that would likely benefit from the enhanced microbial diversity provided through
an intensive multi-donor FMT protocol, ultimately resulting in improved clinical
outcomes such as clinical and endoscopic remission [59].
In a follow up study, Parasmothy et al. sought to better characterize the bacterial and functional changes associated with implementation of FMT in UC patients
to better predict therapeutic success or failure [60]. Analyses of stool faecal samples identified Eubacterium hallii, Roseburia inulinivorans, Eggerthella species,
and Ruminococcus bromii as the strongest predictors in achieving UC remission.
Specific bacterial functional pathways found to be associated with achieving disease remission included benzoate degradation, glycerophospholipid metabolism,
secondary bile acid biosynthesis, SCFA biosynthesis, and starch degradation. Interestingly, microbial taxa that were found to contribute to these pathways included

12 Microbiome Manipulation in Coloproctology 317
https://t.me/med1917
Fig.12.4 (L): Bacteria in
faecal samples most strongly
associated with UC
remission. (R): Bacterial taxa
that contribute to functional
pathways associated with UC
remission
Eubacterium, Ruminococcus, Lachnospiraceae, Roseburia, Dorea, and Coprococcus species, which coincides with the findings of bacterial taxa identified to be
positive predictors of achieving therapeutic success (Fig. 12.4)[60].
Fusobacterium was again identified to be most consistent with therapeutic failure for patients undergoing FMT, in addition to Sutterella, Haemophilus, Escheria,
Megamonas, Clostridium XIVa, Prevotella, Dialister , Veillonella, and Bilophila.
Taken together, the analysis provided in this study identified a subset of microbial taxa and associated metabolic pathways whose presence may best contribute
to, and predict, the success of therapeutic outcomes in patients with active UC
treated with FMT [60]. A Cochrane review of the utility of FMT in ulcerative
colitis analyzed the results of four randomized controlled trials [58]. The use of
FMT in CD was not included, as no randomized controlled trails were identified
that investigated this topic. Based on pooled analyzes from these four studies, the
review concluded that FMT may increase the rates of clinical remission by twofold compared to the control group. In the three studies that assessed gut microbial
manipulations associated with FMT utilization, each study found that FMT was
successfully induced changes in the host microbiome, creating a microenvironment
more similar to that of the healthy faecal donor [58]. Collectively, the implications
of these findings suggest that FMT is successful at addressing host microbiome
dysbiosis and may ultimately represent a reasonable and effective method for
restoring a healthy intestinal microbiome. Further studies are needed to better
address ways in which FMT administration can be optimized and protocolized
to enhance its efficacy for those with UC. The efficacy of FMT in treating CD
also remains uncertain.
12.5.3 Bowel Preparation and Colon Cancer
Many of the studies reviewed in this chapter have highlight the potential for
various bacterial species within the intestinal tract to promote CRC recurrence.
Targeting these potential, cancer-promoting, collagenase-producing organisms in

318 N. R. Suss and B. D. Shogan
https://t.me/med1917
the preoperative setting may serve as a new method to minimize the microbiota’s
role in promoting CRC recurrence. In most institutions, the utilization of combined mechanical bowel preparation (MBP) with oral antibiotics has been adopted
as standard of care for patients undergoing surgical resection. In fact, in its most
recent clinical practice guidelines, The American Society of Colon and Rectal Surgeons provided a strong recommendation (Grade 1B) based on moderate-quality
evidence in favor of the use of MBP with oral antibiotics for elective colorectal
resection, due to reduced rates of surgical site infection, anastomotic leak, readmission, and hospital length of stay [61]. Given that bowel preparation achieves
bacterial decontamination of the colon, it seems reasonable to question whether
it may represent a preoperative method by which to manipulate one’s intestinal
microbiome to reduce CRC recurrence. Gaines et al. found that the use of preoperative antibiotics in human patients was successful at reducing the population
of collagenase-producing E. faecalis and P. mirabilis, that have been attributed to
anastomotic leak and CRC recurrence in mice models [48]. In another study, Zhang
et al. conducted a retrospective cohort study to evaluate the association between
preoperative combined bowel preparation with disease-free survival after surgical
resection for CRC [62]. The primary endpoints of investigation in this study were
CRC recurrence and disease-free survival. In their study, 74.2% of patients did not
receive a combined MBP with antibiotics, whereas 25.8% did. In their propensityscore matched analysis, it was found that receiving a combined MBP with oral
antibiotics was statistically significantly associated with a decreased risk of CRC
recurrence compared to those who did not receive a combined MBP with oral
antibiotics (HR 0.57, 95% CI 0.37–0.89) [62]. Patients receiving a combined MBP
with oral antibiotics were also found to have a statistically significantly higher
5-year disease-free survival compared to those that did not receive preoperative
bowel preparation (p < 0.005). Previous studies, although with varying results,
have demonstrated depletion of bacterial species typically associated with promoting colorectal malignancy with the utilization of preoperative bowel preparation,
such as Peptostreptococcus spp and Enterobacter spp [63, 64]. Taken collectively,
these findings support that the preoperative gut microbiome may play a pivotal,
and potentially even causative, role in promoting postoperative CRC recurrence.
Thus, by manipulating this preoperative intestinal microbiome through the use of
combined MBP and oral antibiotics, CRC recurrences may be reduced. Additionally, numerous studies have demonstrated an association between the utilization of
combined MBP with oral antibiotics and decreased rates of anastomotic leak [61,
65–67]. Given the association between anastomotic leak and CRC recurrence, it
seems logical that preoperative bowel preparation may collectively decrease CRC
recurrence rates through multiple, not mutually exclusive pathways: decreased
anastomotic.

12 Microbiome Manipulation in Coloproctology 319
https://t.me/med1917
12.5.4 Nutritional Prehabilitation and the Intestinal
Microbiome
In the context of this chapter, prehabilitation refers to the utilization of preoperative
nutritional supplementation to modify one’s intestinal microbiome in a way that is
conducive to minimizing the risk of postoperative complications. However, on a
larger scale, preoperative dietary prehabilitation has been studied in the context of
several pathologies, including sepsis and overall postoperative outcomes. As previously discussed, a low-fiber, high-fat Western diet has a deleterious effect on the
intestinal microbiome. In their study, Keskey et al. sought to investigate the efficacy of nutritional prehabilitation with a low-fat, high-fiber diet on the intestinal
microbiome and subsequent postoperative survival and infection [68]. Additionally, their work sought to identify specific measurable biomarkers that could be
quantified to determine whether a healthy gut microbiome was restored following preoperative nutritional prehabilitation in mice. In this study, after being fed a
low-fiber, high-fat Western diet (WD) for six weeks, mice were either continued
on a WD or transitioned to three or seven days of a low-fat, high-fiber standard
chow diet (SD) before undergoing five days of antibiotics, 12 h of starvation, and
a 30% hepatectomy. Preoperative stool microbiota was assessed to help identify a
quantifiable biomarker that could reflect the success of dietary prehabilitation in
reversing the microbial impact of consuming a WD [68]. Faecal measurements of
SCFAs revealed a decrease in the detection of butyrate and acetate within caecal
samples of mice continued on a WD compared to those fed a SD. 16S rRNA gene
sequencing demonstrated a difference in the abundance of bacteria between the SD
and WD fed mice. Bacteroides were found to be much more abundant in mice fed a
SD, whereas Clostridiales was the predominant order in WD fed mice. When analyzing the quantity of enzymes known to play a pivotal role in butyrate metabolism,
it was found that there was an initial reduction in butyrate-producing enzymes with
early SD prehabilitation that was restored by day 7 of prehabilitation. This coincided with the finding that the quantity of butyrate-producing bacteria initially
decreased with early prehabilitation and then subsequently increased as they were
replaced by a new community of butyrate-producing bacteria by day 7 [68]. Given
the known benefits of SCFAs in immune function and post-surgical healing, it thus
makes sense that improvements in surgical outcomes were not seen until day 7 of
prehabilitation. Based on these findings, the authors concluded that the determinantal effects of a WD on the intestinal microbiome can be successfully reversed,
as measured through an increase in butyrate production, with as little as 7 days of
dietary prehabilitation. The implications of this study are profound as the authors
demonstrated that the intestinal microbiome of murine models can be successfully
manipulated, and quantified with the metabolite butyrate, through the use of a
short-term, diet-directed protocol in a way that directly translated into improved
postoperative outcomes. The concept of preoperative nutritional prehabilitation as
it pertains to anastomotic healing and CRC recurrence will be further explored.

320 N. R. Suss and B. D. Shogan
https://t.me/med1917
12.5.5 Impact of Nutritional Prehabilitation on the Intestinal
Microbiota and Anastomotic Healing
Collagenase-producing bacteria, found within the postoperative intestinal microenvironment can inhibit the healing processes and even degrade a new anastomotic
site, allowing for exfoliated tumour cells to migrate across the anastomotic site to
extramucosal regions. Given these findings, there is a need to better characterize
this postoperative gut microbiome to develop methods in which these organisms
can be selectively manipulated, with the goals of reducing anastomotic leakage
and disease recurrence. As diet has been closely associated with intestinal microbiota changes, research has investigated whether preoperative diet can influence
the microbiota at the site of anastomosis.
Hyoju et al. sought to determine the impact of consuming a high-fat Western
diet (WD) versus a low-fat/high-fiber standard chow diet (SD) on the perianastomotic intestinal microbiome and the subsequent impact on anastomotic
healing [69]. To do so, mice were randomized to receive either a WD or SD for
six weeks followed by preoperative antibiotics and distal colectomy with primary
anastomosis. In further experiments, the group fed mice a WD for 6 weeks and
then switched them to a SD for varying amounts of time (2, 4, & 6 weeks) before
colonic resection. Longitudinal stool samples were collected daily for all mice,
and anastomotic healing and intestinal microbiota were analyzed in each set of
studies. The study had numerous significant findings. First, they found that mice
fed a WD diet demonstrated a dominance of Enterococcus, comprising 65–90%
of the microbiota within the first week after surgery, in both expelled stool and
colonic luminal contents [69]. In stark contrast, Enterococcus accounted for 4–
15% of the microbiota in expelled stool and colonic luminal contents in SD-fed
mice. These microbiota changes were found to persist in WD-fed mice for up to
one month postoperatively, whereas Enterococcus could no longer be detected in
SD-fed mice after postoperative day 5. The group then assessed the Enterococcus
identified for collagenolytic activity. While both the WD and SD mice were found
to be equally colonized by collagenolytic populations of Enterococcus on postoperative day three, by day five, the density of collagenolytic Enterococcus had
decreased in SD-fed mice, and increased further in WD-fed mice [69]. Additionally, they found that mice fed a WD had significantly worse anastomotic healing
scores (AHS) compared to those fed a SD diet, which was particularly evident on
postoperative day three and persisted on postoperative day five [69]. It was also
demonstrated that short-term nutritional prehabilitation with a SD after receiving
six weeks of a WD resulted in a significant improvement in anastomotic healing,
independent of the duration the mice were fed the SD (2, 4, or 6 weeks). While
the total abundance of Enterococcus did not vary between the groups fed a strict
WD and those switched to a SD preoperatively, they found a decrease in the collagenolytic activity of the Enterococcus observed in anastomotic tissues for the
mice prehabilitated with a SD for two weeks [69].
Taken collectively, these findings demonstrate the complex interplay between
preoperative diet and subsequent changes in the intestinal microbiota, such that a

12 Microbiome Manipulation in Coloproctology 321
https://t.me/med1917
high-fat diet may enhance the proliferation and survival of collagenase-producing
Enterococcus, an organism previously found to be associated with impaired anastomotic healing and degradation. As has been previously discussed, CRC recurrences
have been closely associated with anastomotic leak. Thus, these findings suggest
that targeting the microbiome to minimize the risk of a poorly healing anastomosis may simultaneously translate to decreased disease recurrence and metastasis..
Of key importance is the finding that the gut microbiota changes influenced by
the consumption of a high-fat diet can be quickly repaired through initiation of a
healthier, high-fiber diet [69]. Based on these findings, whilst the role of nutritional
prehabilitation with a high-fiber diet on anastomotic healing and the subsequent
impact on CRC recurrence remains unknown it presents a future direction for this
work that warrants investigation.
12.6 Conclusion
The “healthy” intestinal microbiome has been implicated in maintaining the homeostasis of nearly every organ system within the human body. However dysbiosis
of this microbiota has the potential to wreak havoc on the underlying biological
systems at play that maintain human function, resulting in the pathogenesis of
several diseases. Research to date has demonstrated mechanisms by which scientists and clinicians can intervene and help revert a state of microbial dysbiosis
to one of symbiosis. With data demonstrating that surgical resection itself can
promote the development of a dysbiotic gut microbiota that promotes CRC recurrence when compounded with additional factors such as a preoperative high-fat
diet, the concept of “prehabilitation” to attenuate the microenvironment conducive
to the growth of tumour-promoting organisms is of current interest. Research to
date has made important contributions to better understanding how various factors
(i.e., nutrition, exercise, psychological support) may simultaneously play a role
in cancer recurrence. However, work to date has not clearly elucidated the rel-
ative impact of such variables or the mechanism underlying the main drivers of
this effect. This area of interest warrants further investigation, with the hope of
one day creating an evidence-based nutritional prehabilitation protocol for patients
who will undergo resection for CRC. Further research in this field may even identify benefits to nutritional prehabilitation as it relates to the intestinal microbiome
for malignancies that extend beyond just CRC.
Acknowledgements All figures that appear throughout this chapter were constructed utilizing
BioRender.com.
References
1. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci.
2019;76:473–93. https://doi.org/10.1007/s00018-018-2943-4.

322 N. R. Suss and B. D. Shogan
https://t.me/med1917
2. Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune
system. Mil Med Res. 2017;4:14. https://doi.org/10.1186/s40779-017-0122-9.
3. Bandeira A, Mota-Santos T, Itohara S, et al. Localization of gamma/delta T cells to the intestinal epithelium i s independent of normal microbial colonization. J Exp Med. 1990;172:239–44.
https://doi.org/10.1084/jem.172.1.239.
4. Ostman S, Rask C, Wold AE, et al. Impaired regulatory T cell function in germ-free mice. Eur
J Immunol. 2006;36:2336–46. https://doi.org/10.1002/eji.200535244.
5. Knox NC, Forbes JD, Peterson C-L, et al. The gut microbiome in inflammatory bowel disease:
lessons learned from other immune-mediated inflammatory diseases. Am J Gastroenterol.
2019;114:1051–70. https://doi.org/10.14309/ajg.0000000000000305.
6. Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of
inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152:327–
39. https://doi.org/10.1053/j.gastro.2016.10.012.
7. Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease.
J Allergy Clin Immunol. 2020;145:16–27. https://doi.org/10.1016/j.jaci.2019.11.003.
8. Wlodarska M, Luo C, Kolde R, et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host Microbe. 2017;22:25-37.e6. https://doi.
org/10.1016/j.chom.2017.06.007.
9. Wang Y, Nguyen LH, Mehta RS, et al. Association between the sulfur microbial diet and risk
of colorectal cancer. JAMA Netw Open. 2021;4: e2134308. https://doi.org/10.1001/jamanetwo
rkopen.2021.34308.
10. Mouries J, Brescia P, Silvestri A, et al. Microbiota-driven gut vascular barrier disruption is
a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019;71:1216–28.
https://doi.org/10.1016/j.jhep.2019.08.005.
11. Gaines S, Shao C, Hyman N, Alverdy JC. Gut microbiome influences on anastomotic leak and
recurrence rates following colorectal cancer surgery. Br J Surg. 2018;105:e131–41. https://doi.
org/10.1002/bjs.10760.
12. Shogan BD, Belogortseva N, Luong PM, et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med.
2015;7:286ra68. https://doi.org/10.1126/scitranslmed.3010658.
13. Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome.
Nat Biotechnol. 2014;32:834–41. https://doi.org/10.1038/nbt.2942.
14. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med.
2016;375:2369–79. https://doi.org/10.1056/NEJMra1600266.
15. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal
proteins involved in innate immunity. Nat Immunol. 2003;4:269–73. https://doi.org/10.1038/
ni888.
16. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health.
BMJ. 2018;361: k2179. https://doi.org/10.1136/bmj.k2179.
17. Long SL, Gahan CGM, Joyce SA. Interactions between gut bacteria and bile in health and
disease. Mol Aspects Med. 2017;56:54–65. https://doi.org/10.1016/j.mam.2017.06.002.
18. Bäckhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism in the human intestine.
Science. 2005;307:1915–20. https://doi.org/10.1126/science.1104816.
19. Nardone G, Compare D. The human gastric microbiota: is it time to rethink the pathogenesis of
stomach diseases? United European Gastroenterol J. 2015;3:255–60. https://doi.org/10.1177/
2050640614566846.
20. El Aidy S, van den Bogert B, Kleerebezem M. The small intestine microbiota, nutritional
modulation and relevance for health. Curr Opin Biotechnol. 2015;32:14–20. https://doi.org/10.
1016/j.copbio.2014.09.005.
21. Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal
microbiome and their effects on human health. Gastroenterology. 2014;146:1449–58. https://
doi.org/10.1053/j.gastro.2014.01.052.

12 Microbiome Manipulation in Coloproctology 323
https://t.me/med1917
22. Britton GJ, Contijoch EJ, Mogno I, et al. Microbiotas from humans with inflammatory bowel
disease alter the balance of gut Th17 and RORγt+ regulatory t cells and exacerbate colitis in
mice. Immunity. 2019;50:212-224.e4. https://doi.org/10.1016/j.immuni.2018.12.015.
23. Rutgeerts P, Goboes K, Peeters M, et al. Effect of faecal stream diversion on recurrence of
Crohn’s disease in the neoterminal ileum. Lancet. 1991;338:771–4. https://doi.org/10.1016/
0140-6736(91)90663-a.
24. Harper PH, Lee EC, Kettlewell MG, et al. Role of the faecal stream in the maintenance of
Crohn’s colitis. Gut. 1985;26:279–84. https://doi.org/10.1136/gut.26.3.279.
25. Gevers D, Kugathasan S, Denson LA, et al. The treatment-naive microbiome in new-onset
Crohn’s disease. Cell Host Microbe. 2014;15:382–92. https://doi.org/10.1016/j.chom.2014.
02.005.
26. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory
commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc
Natl Acad Sci USA. 2008;105:16731–6. https://doi.org/10.1073/pnas.0804812105.
27. Rajca S, Grondin V, Louis E, et al. Alterations in the intestinal microbiome (dysbiosis) as
a predictor of relapse after infliximab withdrawal in Crohn’s disease. Inflamm Bowel Dis.
2014;20:978–86. https://doi.org/10.1097/MIB.0000000000000036.
28. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin.
2018;68:394–424. https://doi.org/10.3322/caac.21492.
29. Jeffery M, Hickey BE, Hider PN, See AM (2016) Follow-up strategies for patients treated for
non-metastatic colorectal cancer. Cochrane Database Syst Rev. 11:CD002200. https://doi.org/
10.1002/14651858.CD002200.pub3.
30. Ryuk JP, Choi G-S, Park JS, et al. Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Ann Surg Treat Res. 2014;86:143–51.
https://doi.org/10.4174/astr.2014.86.3.143.
31. Thomas RM. Role of bacteria in the development of colorectal cancer. Clin Colon Rectal Surg.
2023;36:105–11. https://doi.org/10.1055/s-0042-1760679.
32. Nguyen LH, Ma W, Wang DD, et al. Association between sulfur-metabolizing bacterial communities in stool and risk of distal colorectal cancer in men. Gastroenterology. 2020;158:1313–
25. https://doi.org/10.1053/j.gastro.2019.12.029.
33. Chen H-M, Yu Y-N, Wang J-L, et al. Decreased dietary fiber intake and structural alteration of
gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr. 2013;97:1044–
52. https://doi.org/10.3945/ajcn.112.046607.
34. Chen D, Jin D, Huang S, et al. Clostridium butyricum, a butyrate-producing probiotic, inhibits
intestinal tumour development through modulating Wnt signaling and gut microbiota. Cancer
Lett. 2020;469:456–67. https://doi.org/10.1016/j.canlet.2019.11.019.
35. Liu L, Dong W, Wang S, et al. Deoxycholic acid disrupts the intestinal mucosal barrier and
promotes intestinal tumourigenesis. Food Funct. 2018;9:5588–97. https://doi.org/10.1039/c8f
o01143e.
36. Ma Y, Zhang Y, Qu R, et al. Promotion of deoxycholic acid effect on colonic cancer cell lines
in vitro by altering the mucosal microbiota. Microorganisms. 2022;10:2486. https://doi.org/10.
3390/microorganisms10122486.
37. Song X, An Y, Chen D, et al. Microbial metabolite deoxycholic acid promotes vasculogenic
mimicry formation in intestinal carcinogenesis. Cancer Sci. 2022;113:459–77. https://doi.org/
10.1111/cas.15208.
38. Schmitt FCF, Schneider M, Mathejczyk W, et al. Postoperative complications are associated
with long-term changes in the gut microbiota following colorectal cancer surgery. Life (Basel).
2021;11:246. https://doi.org/10.3390/life11030246.
39. Yu S-Y, Xie Y-H, Qiu Y-W, et al. Moderate alteration to gut microbiota brought by colorectal adenoma resection. J Gastroenterol Hepatol. 2019;34:1758–65. https://doi.org/10.1111/jgh.
14735.
40. Cass S, White MG. The influence of the microbiome on metastatic colorectal cancer. Clin
Colon Rectal Surg. 2023;36:112–9. https://doi.org/10.1055/s-0043-1760864.

324 N. R. Suss and B. D. Shogan
https://t.me/med1917
41. Goto S, Hasegawa S, Hida K, et al. Multicenter analysis of impact of anastomotic leakage on long-term oncologic outcomes after curative resection of colon cancer. Surgery.
2017;162:317–24. https://doi.org/10.1016/j.surg.2017.03.005.
42. Pietra N, Sarli L, Thenasseril BJ, et al. Risk factors of local recurrence of colorectal cancer: a
multivariate study. Hepatogastroenterology. 1998;45:1573–8.
43. Dragutinovi´c VV, Radonji´c NV, Petronijevi´c ND, et al. Matrix metalloproteinase-2 (MMP-2)
and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with
colorectal cancer. Mol Cell Biochem. 2011;355:173–8. https://doi.org/10.1007/s11010-011-
0851-0.
44. Said AH, Raufman J-P, Xie G. The role of matrix metalloproteinases in colorectal cancer.
Cancers (Basel). 2014;6:366–75. https://doi.org/10.3390/cancers6010366.
45. Belogortseva N, Krezalek M, Guyton K, et al. Media from macrophages co-incubated with
Enterococcus faecalis induces epithelial cell monolayer reassembly and altered cell morphology. PLoS ONE. 2017;12: e0182825. https://doi.org/10.1371/journal.pone.0182825.
46. Olivas AD, Shogan BD, Valuckaite V, et al. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa t hat enhances its virulence: possible role in anastomotic leak. PLoS ONE.
2012;7: e44326. https://doi.org/10.1371/journal.pone.0044326.
47. Meyerhardt JA, Niedzwiecki D, Hollis D, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007;298:754–64.
https://doi.org/10.1001/jama.298.7.754.
48. Gaines S, van Praagh JB, Williamson AJ, et al. Western diet promotes intestinal colonization
by collagenolytic microbes and promotes tumour formation after colorectal surgery. Gastroenterology. 2020;158:958-970.e2. https://doi.org/10.1053/j.gastro.2019.10.020.
49. Ordóñez-Morán P, Huelsken J. Complex metastatic niches: already a target for therapy? Curr
Opin Cell Biol. 2014;31:29–38. https://doi.org/10.1016/j.ceb.2014.06.012.
50. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer.
2009;9:285–93. https://doi.org/10.1038/nrc2621.
51. Spadoni I, Zagato E, Bertocchi A, et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science. 2015;350:830–4. https://doi.org/10.1126/science.aad0135.
52. Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal
bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021;39:708-
724.e11. https://doi.org/10.1016/j.ccell.2021.03.004.
53. Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358:1443–8. https://doi.org/10.1126/science.
aal5240.
54. Cheng Y-W, Fischer M. Faecal microbiota transplantation. Clin Colon Rectal Surg.
2023;36:151–6. https://doi.org/10.1055/s-0043-1760865.
55. Wilson KH, Perini F. Role of competition for nutrients in suppression of Clostridium difficile
by the colonic microflora. Infect Immun. 1988;56:2610–4. https://doi.org/10.1128/iai.56.10.
2610-2614.1988.
56. Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016;13:508–16. https://doi.org/10.1038/nrgastro.201
6.98.
57. Weingarden AR, Dosa PI, DeWinter E, et al. Changes in colonic bile acid composition following faecal microbiota transplantation are sufficient to control clostridium difficile germination
and growth. PLoS ONE. 2016;11: e0147210. https://doi.org/10.1371/journal.pone.0147210.
58. Imdad A, Nicholson MR, Tanner-Smith EE, et al. Faecal transplantation for treatment of
inflammatory bowel disease. Cochrane Database Syst Rev. 2018;11:CD012774. https://doi.
org/10.1002/14651858.CD012774.pub2.
59. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota
transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet.
2017;389:1218–28. https://doi.org/10.1016/S0140-6736(17)30182-4.

12 Microbiome Manipulation in Coloproctology 325
https://t.me/med1917
60. Paramsothy S, Nielsen S, Kamm MA, et al. Specific bacteria and metabolites associated with
response to faecal microbiota transplantation in patients with ulcerative colitis. Gastroenterology. 2019;156:1440-1454.e2. https://doi.org/10.1053/j.gastro.2018.12.001.
61. Migaly J, Bafford AC, Francone TD, et al. The American society of colon and rectal surgeons
clinical practice guidelines for the use of bowel preparation in elective colon and rectal surgery.
Dis Colon Rectum. 2019;62:3–8. https://doi.org/10.1097/DCR.0000000000001238.
62. Zhang LM, Schuitevoerder D, White MG, et al. Combined mechanical and oral antibiotic
bowel preparation is associated with prolonged recurrence-free survival following surgery for
colorectal cancer. J Surg Oncol. 2021;124:1106–14. https://doi.org/10.1002/jso.26619.
63. Watanabe M, Murakami M, Nakao K, et al. Randomized clinical trial of the influence of
mechanical bowel preparation on faecal microflora in patients undergoing colonic cancer
resection. Br J Surg. 2010;97:1791–7. https://doi.org/10.1002/bjs.7253.
64. Long X, Wong CC, Tong L, et al. Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity. Nat Microbiol. 2019;4:2319–30. https://doi.org/10.
1038/s41564-019-0541-3.
65. Scarborough JE, Mantyh CR, Sun Z, Migaly J. Combined mechanical and oral antibiotic bowel
preparation reduces incisional surgical site infection and anastomotic leak rates after elective
colorectal resection: an analysis of colectomy-targeted ACS NSQIP. Ann Surg. 2015;262:331–
7. https://doi.org/10.1097/SLA.0000000000001041.
66. Clarke JS, Condon RE, Bartlett JG, et al. Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study. Ann
Surg. 1977;186:251–9. https://doi.org/10.1097/00000658-197709000-00003.
67. Kiran RP, Murray ACA, Chiuzan C, et al. Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and
ileus after colorectal surgery. Ann Surg. 2015;262:416–425; discussion 423–425. https://doi.
org/10.1097/SLA.0000000000001416.
68. Keskey R, Papazian E, Lam A, et al. Defining microbiome readiness for surgery: dietary
prehabilitation and stool biomarkers as predictive tools to improve outcome. Ann Surg.
2022;276:e361–9. https://doi.org/10.1097/SLA.0000000000004578.
69. Hyoju SK, Adriaansens C, Wienholts K, et al. Low-fat/high-fibre diet prehabilitation improves
anastomotic healing via the microbiome: an experimental model. Br J Surg. 2020;107:743–55.
https://doi.org/10.1002/bjs.11388.
Соседние файлы в папке @xirurgi_2025
